Method of using hydroxycarboxylic acids or related compounds for treating skin changes asociated with intrinsic and extrinsic aging

ABSTRACT

A composition comprising an amphoteric or pseudo-amphoteric agent and a polyhydroxy alpha hydroxyacid existing as a free acid, lactone, or salt, and isomeric or non-isomeric forms thereof is provided. The amphoteric or pseudo-amphoteric agent can be selected from amino acids, dipeptides, aminoaldonic acid, aminouronic acid, lauryl aminoproplyglycine, aminoaldaric acid, neuraminic acid desulfated heparin, deacetylated hyaluronic acid, hyalobiuronic acid, chondrosine, deacetylated chondroitin, creatine, creatinine, hydroxyproline, homocysteine, homocystine, homoserine, ornithine, citrulline, phosphatidylserine, and sphingomyelin. The composition may contain other additives, including cosmetic or pharmaceutical agents for topical treatment of dermatological disorders.

FIELD OF THE INVENTION

[0001] This invention relates generally to therapeutic treatment as wellas preventive measures for cosmetic conditions and dermatologicdisorders by topical administration of amphoteric compositions orpolymeric forms of alpha hydroxyacids, alpha ketoacids and relatedcompounds. We initially discovered that alpha hydroxy or keto acids andtheir derivatives were effective in the topical treatment of diseaseconditions such as dry skin, ichthyosis, eczema, palmar and plantarhyperkeratoses, dandruff, acne and warts.

[0002] We have now discovered that amphoteric compositions and polymericforms of alpha hydroxyacids, alpha ketoacids and related compounds ontopical administration are therapeutically effective for variouscosmetic conditions and dermatologic disorders.

BRIEF DESCRIPTION OF THE PRIOR ART

[0003] In our prior U.S. Pat. No. 3,879,537 entitled “Treatment ofIchthyosiform Dermatoses” we described and claimed the use of certainalpha hydroxyacids, alpha ketoacids and related compounds for topicaltreatment of fish-scale like ichthyotic conditions in humans. In ourU.S. Pat. No. 3,920,835 entitled “Treatment of Disturbed Keratinization”we described and claimed the use of these alpha hydroxyacids, alphaketoacids and their derivatives for topical treatment of dandruff, acne,and palmar and plantar hyperkeratosis.

[0004] In our prior U.S. Pat. No. 4,105,783 entitled “Treatment of DrySkin” we described and claimed the use of alpha hydroxyacids, alphaketoacids and their derivatives for topical treatment of dry skin. Inour recent U.S. Pat. No. 4,246,261 entitled “Additives Enhancing TopicalCorticosteroid Action” we described and claimed that alpha hydroxyacids,alpha ketoacids and their derivatives, could greatly enhance thetherapeutic efficacy of corticosteroids in topical treatment ofpsoriasis, eczema, seborrheic dermatitis and other inflammatory skinconditions.

[0005] In our more recent U.S. Pat. No. 4,363,815 entitled “AlphaHydroxyacids, Alpha Ketoacids and Their Use in Treating Skin Conditions”we described and claimed that alpha hydroxyacids and alpha ketoacidsrelated to or originating from amino acids, whether or not found inproteins, were effective in topical treatment of skin disordersassociated with disturbed keratinization or inflammation. These skindisorders include dry skin, ichthyosis, palmar and plantarhyperkeratosis, dandruff, Darier's disease, lichen simplex chronicus,keratoses, acne, psoriasis, eczema, pruritus, warts and herpes.

[0006] In our most recent patent application Ser. No. 945,680 filed Dec.23, 1986 and entitled “Additives Enhancing Topical Actions ofTherapeutic Agents” we described and claimed that incorporation of analpha hydroxyacid or related compound can substantially enhancetherapeutic actions of cosmetic and pharmaceutical agents.

SUMMARY OF THE INVENTION

[0007] There is no doubt that alpha hydroxyacids, alpha ketoacids andrelated compounds are therapeutically effective for topical treatment ofvarious cosmetic conditions and dermatologic disorders including dryskin, acne, dandruff, keratoses, age spots, wrinkles and disturbedkeratinization. However, the compositions containing these acids mayirritate human skin on repeated topical applications due to lower pH ofthe formulations. The irritation may range from a sensation of tingling,itching and burning to clinical signs of redness and peeling. Causes forsuch irritation may arise from the following:

[0008] Upper layers of normal skin have a pH of 4.2 to 5.6, but thecompositions containing most alpha hydroxyacids or alpha ketoacids havepH values of less than 3.0. For example, a topical formulationcontaining 7.6% (1 M) glycolic acid has a pH of 1.9, and a compositioncontaining 9% (1 M) lactic acid has the same pH of 1.9. Thesecompositions of lower pH on repeated topical applications can cause adrastic pH decrease in the stratum corneum of human skin, and provokedisturbances in intercorneocyte bondings resulting in adverse skinreactions, especially to some individuals with sensitive skin.

[0009] Moreover, with today's state of the art it is still verydifficult to formulate a lotion, cream or ointment emulsion whichcontains a free acid form of the alpha hydroxyacid, and which isphysically stable as a commercial product for cosmetic or pharmaceuticaluse.

[0010] When a formulation containing an alpha hydroxyacid or alphaketoacid is reacted equimolarly or equinormally with a metallic alkalisuch as sodium hydroxide or potassium hydroxide the composition becomestherapeutically ineffective. The reasons for such loss of therapeuticeffects are believed to be as follows:

[0011] The intact skin of humans is a very effective barrier to manynatural and synthetic substances. Cosmetic and pharmaceutical agents maybe pharmacologically effective by oral or other systematicadministration, but many of them are much less or totally ineffective ontopical application to the skin. Topical effectiveness of apharmaceutical agent depends on two major factors; (a) bioavailabilityof the active ingredient in the topical preparation and (b) percutaneousabsorption, penetration and distribution of the active ingredient to thetarget site in the skin. For example, a topical preparation containing5% salicylic acid is therapeutically effective as a keratolytic, butthat containing 5% sodium salicylate is not an effective product. Thereason for such difference is that salicylic acid is in bioavailableform and can penetrate the stratum corneum, but sodium salicylate is notin bioavailable form and cannot penetrate the stratum corneum of theskin.

[0012] In the case of alpha hydroxyacids, a topical preparationcontaining 5% glycolic acid is therapeutically effective for dry skin,but that containing 5% sodium glycollate is not effective. The same istrue in case of 5% lactic acid versus 5% sodium lactate. The reason forsuch difference is that both glycolic acid and lactic acid are inbioavailable forms and can readily penetrate the stratum corneum, butsodium glycollate and sodium lactate are not in bioavailable forms andcannot penetrate the stratum corneum of the skin.

[0013] When a formulation containing an alpha hydroxyacid or alphaketoacid is reacted equimolarly or equinormally with ammonium hydroxideor an organic base of smaller molecule the composition still shows sometherapeutic effects for certain cosmetic conditions such as dry skin,but the composition has lost most of its potency for other dermatologicdisorders such as wrinkles, keratoses, age spots and skin changesassociated with aging.

[0014] It has now been discovered that amphoteric compositionscontaining alpha hydroxyacids, alpha ketoacids or related compounds, andalso the compositions containing dimeric or polymeric forms ofhydroxyacids overcome the aforementioned shortcomings and retain thetherapeutic efficacies for cosmetic conditions and dermatologicdisorders. The amphoteric composition contains in combination anamphoteric or pseudoamphoteric compound and at least one of the alphahydroxyacids, alpha ketoacids or related compounds. Such amphotericsystem has a suitable pH, and can release the active form of an alphahydroxyacid or alpha ketoacid into the skin. The dimeric and polymericforms of alpha, beta or other hydroxyacids in non-aqueous compositionshave a more desired pH than that of the monomeric form of thehydroxyacids. The non-aqueous compositions can be formulated and inducedto release the active form of hydroxyacids after the compositions havebeen topically applied to the skin. The cosmetic conditions anddermatologic disorders in humans and animals, in which the amphotericcompositions containing the dimeric or polymeric forms of hydroxyacidsmay be useful, include dry skin, dandruff, acne, keratoses, psoriasis,eczema, pruritus, age spots, lentigines, melasmas, wrinkles, warts,blemished skin, hyperpigmented skin, hyperkeratotic skin, inflammatorydermatoses, skin changes associated with aging and as skin cleansers.

DETAILED DESCRIPTION OF THE INVENTION I. Amphoteric and PseudoamphotericCompositions

[0015] Amphoteric substances by definition should behave either as anacid or a base, and can be an organic or an inorganic compound. Themolecule of an organic amphoteric compound should consist of at leastone basic and one acidic group. The basic groups include, for example,amino, imino and guanido groups. The acidic groups include, for example,carboxylic, phosphoric and sulfonic groups. Some examples of organicamphoteric compounds are amino acids, peptides, polypeptides, proteins,creatine, aminoaldonic acids, aminouronic acids, laurylaminopropylglycine, aminoaldaric acids, neuraminic acid, desulfatedheparin, deacetylated hyaluronic acid, hyalobiuronic acid, chondrosineand deacetylated chondroitin.

[0016] Inorganic amphoteric compounds are certain metallic oxides suchas aluminum oxide and zinc oxide.

[0017] Pseudoamphoteric compounds are either structurally related totrue amphoteric compounds or capable of inducing the same function whenthey are incorporated into the compositions containing alphahydroxyacids or ketoacids. Some examples of pseudoamphoteric compoundsare creatinine, stearamidoethyl diethylamine, stearamidoethyldiethanolamine, stearamidopropyl dimethylamine, quaternary ammoniumhydroxide and quaternium hydroxide.

[0018] The amphoteric composition of the instant invention contains incombination an alpha hydroxyacid or alpha ketoacid and an amphoteric orpseudoamphoteric compound. There are two advantages of utilizing anamphoteric or the like compound in the therapeutic compositioncontaining an alpha hydroxy or ketoacid. These are (a) the overall pH ofthe composition is raised, so that the composition becomes less ornon-irritating to the skin and (b) some alpha hydroxy or ketoacidmolecules react with the amphoteric compound to form a quadruple ioniccomplex which acts as buffering system to control the release of alphahydroxy or ketoacid into the skin, therefore, eliminating the skinirritation and still retaining the therapeutic efficacies.

[0019] The following are some examples. 2-Hydroxyethanoic acid (glycolicacid) 1 M aqueous solution has pH 1.9. The pHs of compositions change to3.0 and 3.2 when arginine 0.5 M and creatinine 0.5 M respectively areincorporated into the formulations. 2-Hydroxypropanoic acid (lacticacid) 1 M aqueous solution has pH 1.9. The pHs of compositions change to3.1 and 6.9 when arginine 0.5 M and 1.0 M respectively are incorporatedinto the formulations. 2-Methyl 2-hydroxypropanoic acid (methyllacticacid) 1 M aqueous solution has pH 1.9. The pHs of compositions change to3.3, 3.4 and 3.2 when 0.5 M each of arginine, creatinine and4-aminobutanoic acid respectively are incorporated into theformulations. 2-Hydroxybutane-1,4-dioic acid (malic acid) 1 M aqueoussolution has pH 1.8, but the pH of the composition changes to 3.0 whencreatinine 0.5 M is incorporated into the formulation.

[0020] Ideally, an amphoteric compound should contain both anionic andcationic groups or functional groups capable of behaving both as an acidand a base. Although inorganic amphoteric compounds such as aluminumoxide, aluminum hydroxide and zinc oxide may be utilized, organicamphoteric compounds have been found to be more efficient in formulatingtherapeutic compositions of the instant invention.

[0021] Organic amphoteric and pseudoamphoteric compounds may beclassified into three groups, namely (a) amino acid type, (b)imidazoline and lecithin amphoterics and (c) pseudoamphoterics andmiscellaneous amphoterics.

[0022] (a) Amino acid type amphoterics. Amphoteric compounds of aminoacid type include all the amino acids, dipeptides, polypeptides,proteins and the like which contain at least one of the basic groupssuch as amino, imino, guanido, imidazolino and imidazolyl, and one ofthe acidic groups such as carboxylic, sulfonic, sulfinic and sulfate.

[0023] Glycine is a simple amphoteric compound which contains only oneamino group and one carboxylic group. Lysine contains two amino groupsand one carboxylic group. Aspartic acid contains one amino group and twocarboxylic groups. Arginine contains one amino group, one guanido groupand one carboxylic group. Histidine contains one amino group, oneimidazolyl group and one carboxylic group. Taurine contains one aminogroup and one sulfonic group. Cysteine sulfinic acid contains one aminogroup, one carboxylic group and one sulfinic group. The amino group ofan amphoteric compound may also be substituted, such as in betaine whichis a glycine N,N,N-trimethyl inner salt.

[0024] Glycylglycine is a simple dipeptide which contains one free aminogroup and one free carboxylic group. Glycylhistidine is also a dipeptidewhich contains one free amino group, one imidazolyl group and one freecarboxylic group.

[0025] The representative amphoteric compounds of amino acid type may belisted as follows: Glycine, alanine, valine, leucine, isoleucine,serine, threonine, cysteine, cystine, methionine, aspartic acid,asparagine, glutamic acid, glutamine, arginine, lysine, 5-hydroxylysine,histidine, phenylalanine, tyrosine, tryptophan, 3-hydroxyproline,4-hydroxyproline and proline.

[0026] The related amino acids include homocysteine, homocystine,homoserine, ornithine, citrulline, creatine, 3-aminopropanoic acid,theanine, 2-aminobutanoic acid, 4-aminobutanoic acid,2-amino-2-methylpropanoic acid, 2-methyl-3-aminopropanoic acid,2,6-diaminopimelic acid, 2-amino-3-phenylbutanoic acid, phenylglycine,canavanine, canaline, 4-hydroxyarginine, 4-hydroxyornithine,homoarginine, 4-hydroxyhomoarginine, β-lysine, 2,4-diaminobutanoic acid,2,3-diaminopropanoic acid, 2-methylserine, 3-phenylserine and betaine.

[0027] Sulfur-containing amino acids include taurine, cysteinesulfinicacid, methionine sulfoxide and methionine sulfone.

[0028] The halogen-containing amino acids include 3,5-diiodotyrosine,thyroxine and monoiodotyrosine. The imino type acids include pipecolicacid, 4-aminopipecolic acid and 4-methylproline.

[0029] The dipeptides include for example, glycylglycine, carnosine,anserine, ophidine, homocarnosine, β-alanyllysine, β-alanylarginine. Thetripeptides include for example, glutathione, ophthalmic acid andnorophthalmic acid. Short-chain polypeptides of animal, plant andbacterial origin containing up to 100 amino acid residues includebradykinin and glucagon. The preferred proteins include for exampleprotamines, histones and other lysine and arginine rich proteins.

[0030] (b) Imidazoline and lecithin amphoterics. The amphotericcompounds of imidazoline derived type are commercially synthesized from2-substituted-2-imidazolines obtained by reacting a fatty acid with anaminoethylethanolamine. These amphoterics include cocoamphoglycine,cocoamphopropionate, and cocoamphopropylsulfonate. The amphotericcompounds of lecithin and related type include for example, phosphatidylethanolamine, phosphatidyl serine and sphingomyelin.

[0031] (c) Pseudoamphoterics and miscellaneous amphoterics. Manypseudoamphoteric compounds are chemically related or derived from trueamphoterics. For example, creatinine is derived from creatine. Otherpseudoamphoteric compounds may include fatty amide amines such asstearamidoethyl diethylamine, stearamidoethyl diethanolamine andstearamidopropyl dimethylamine. Other pseudoamphoteric related compoundsinclude quaternary ammonium hydroxide and quaternium hydroxide.

[0032] In accordance with the present invention, the alpha hydroxyacid,the alpha ketoacids and the related compounds which are incorporatedinto amphoteric or pseudoamphoteric compositions for cosmetic conditionsand dermatologic disorders may be classified into three groups.

[0033] The first group is organic carboxylic acids in which one hydroxylgroup is attached to the alpha carbon of the acids. The genericstructure of such alpha hydroxyacids may be represented as follows:

(Ra) (Rb) C (OH) COOH

[0034] where Ra and Rb are H, F, Cl, Br, alkyl, aralkyl or aryl group ofsaturated or unsaturated, isomeric or non-isomeric, straight or branchedchain or cyclic form, having 1 to 25 carbon atoms, and in addition Raand Rb may carry OH, CHO, COOH and alkoxy group having 1 to 9 carbonatoms. The alpha hydroxyacids may be present as a free acid or lactoneform, or in a salt form with an organic base or an inorganic alkali. Thealpha hydroxyacids may exist as stereoisomers as D, L, and DL forms whenRa and Rb are not identical.

[0035] Typical alkyl, aralkyl and aryl groups for Ra and Rb includemethyl, ethyl, propyl, isopropyl, butyl, pentyl, octyl, lauryl, stearyl,benzyl and phenyl, etc. The alpha hydroxyacids of the first group may bedivided into (1) alkyl alpha hydroxyacids, (2) aralkyl and aryl alphahydroxyacids, (3) polyhydroxy alpha hydroxyacids, and (4) polycarboxylicalpha hydroxyacids. The following are representative alpha hydroxyacidsin each subgroup.

[0036] (1) Alkyl Alpha Hydroxyacids

[0037] 1. 2-Hydroxyethanoic acid (Glycolic acid, hydroxyacetic acid)

[0038] (H) (H) C (OH) COOH

[0039] 2. 2-Hydroxypropanoic acid (Lactic acid)

[0040] (CH₃) (H) C (OH) COOH

[0041] 3. 2-Methyl 2-hydroxypropanoic acid (Methyllactic acid)

[0042] (CH₃) (CH₃) C (OH) COOH

[0043] 4. 2-Hydroxybutanoic acid

[0044] (C₂H₅) (H) C (OH) COOH

[0045] 5. 2-Hydroxypentanoic acid

[0046] (C₃H₇) (H) C (OH) COOH

[0047] 6. 2-Hydroxyhexanoic acid

[0048] (C₄H₉) (H) C (OH) COOH

[0049] 7. 2-Hydroxyheptanoic acid

[0050] (C₅H₁₁ (H) C (OH) COOH

[0051] 8. 2-Hydroxyoctanoic acid

[0052] (C₆H₁₃) (H) C (OH) COOH

[0053] 9. 2-Hydroxynonanoic acid

[0054] (C₇H₁₅) (H) C (OH) COOH

[0055] 10. 2-Hydroxydecanoic acid

[0056] C₈H₁₇) (H) C (OH) COOH

[0057] 11. 2-Hydroxyundecanoic acid

[0058] (C₉H₁₉) (H) C (OH) COOH

[0059] 12. 2-Hydroxydodecanoic acid (Alpha hydroxylauric acid)

[0060] (C₁₀H₂₁) (H) C (OH) COOH

[0061] 13. 2-Hydroxytetradecanoic acid (Alpha hydroxymyristic acid)

[0062] (C₁₂H₂₅) (H) C (OH) COOH

[0063] 14. 2-Hydroxyhexadecanoic acid (Alpha hydroxypalmitic acid)

[0064] C₁₄H₂₉) (H) C (OH) COOH

[0065] 15. 2-Hydroxyoctadecanoic acid (Alpha hydroxystearic acid)

[0066] (C₁₆H₃₄) (H) C (OH) COOH

[0067] 16. 2-Hydroxyeicosanoic acid (Alpha hydroxyarachidonic acid)

[0068] (C₁₈H₃₇) (H) C (OH) COOH

[0069] (2) Aralkyl And Aryl Alpha Hydroxyacids

[0070] 1. 2-Phenyl 2-hydroxyethanoic acid (Mandelic acid)

[0071] (C₆H₅) (H) C (OH) COOH

[0072] 2. 2,2-Diphenyl 2-hydroxyethanoic acid (Benzilic acid)

[0073] (C₆H₅) (C₆H₅) C (OH) COOH

[0074] 3. 3-Phenyl 2-hydroxypropanoic acid (Phenyllactic acid)

[0075] (C₆H₅CH₂) (H) C (OH) COOH

[0076] 4. 2-Phenyl 2-methyl 2-hydroxyethanoic acid (Atrolactic acid)

[0077] (C₆H₅) (CH₃) C (OH) COOH

[0078] 5. 2-(4′-Hydroxyphenyl) 2-hydroxyethanoic acid (4-Hydroxymandelicacid)

[0079] (HO—C₆H₄) (H) C (OH) COOH

[0080] 6. 2-(4′-Chlorophenyl) 2-hydroxyethanoic acid (4-Chloromandelicacid)

[0081] (Cl—C₆H₄) (H) C (OH) COOH

[0082] 7. 2-(3′-Hydroxy-4′-methoxyphenyl) 2-hydroxyethanoic acid(3-Hydroxy-4-methoxymandelic acid)

[0083] (HO—,CH₃O—C₆H₃) (H) C (OH) COOH

[0084] 8. 2-(4′-Hydroxy-3′-methoxyphenyl) 2-hydroxyethanoic acid(4-Hydroxy-3-methoxymandelic acid)

[0085] (HO—,CH₃O—C₆H₃) (H) C (OH) COOH

[0086] 9. 3-(2′-Hydroxyphenyl) 2-hydroxypropanoic acid[3-(2′-Hydroxyphenyl) lactic acid]

[0087] HO—C₆H₄—CH₂(H) C (OH) COOH

[0088] 10. 3-(4′-Hydroxyphenyl) 2-hydroxypropanoic acid[3-(4′-Hydroxyphenyl) lactic acid)]

[0089] HO—C₆H₄—CH₂ (H) C (OH) COOH

[0090] 11. 2-(3′,4′-Dihydroxyphenyl) 2-hydroxyethanoic acid(3,4-Dihydroxymandelic acid)

[0091] HO—,HO—C₆H₃ (H) C (OH) COOH

[0092] (3) Polyhydroxy Alpha Hydroxyacids

[0093] 1. 2,3-Dihydroxypropanoic acid (Glyceric acid)

[0094] (HOCH₂) (H) C (OH) COOH

[0095] 2. 2,3,4-Trihydroxybutanoic acid (Isomers; erythronic acid,threonic acid)

[0096] HOCH₂ (HO)CH₂ (H) C (OH) COOH

[0097] 3. 2,3,4,5-Tetrahydroxypentanoic acid (Isomers; ribonic acid,arabinoic acid, xylonic acid, lyxonic acid)

[0098] HOCH₂ (HO)CH₂ (HO)CH₂ (H) C (OH) COOH

[0099] 4. 2,3,4,5,6-Pentahydroxyhexanoic acid (Isomers; allonic acid,altronic acid, gluconic acid, mannoic acid, gulonic acid, idonic acid,galactonic acid, talonic acid)

[0100] HOCH₂ (HO)CH₂ (HO)CH₂ (HO)CH₂ (H) C (OH) COOH

[0101] 5. 2,3,4,5,6,7-Hexahydroxyheptanoic acid (Isomers; glucoheptonicacid, galactoheptonic acid etc.)

[0102] HOCH₂ (HO)CH₂ (HO)CH₂ (HO)CH₂ (HO)CH₂ (H) C (OH) COOH

[0103] (4) Polycarboxylic Alpha Hydroxyacids

[0104] 1. 2-Hydroxypropane-1,3-dioic acid (Tartronic acid)

[0105] HOOC (H) C (OH) COOH

[0106] 2. 2-Hydroxybutane-1,4-dioic acid (Malic acid)

[0107] HOOC CH₂ (H) C (OH) COOH

[0108] 3. 2,3-Dihydroxybutane-1,4-dioic acid (Tartaric acid)

[0109] HOOC (HO)CH (H) C (OH) COOH

[0110] 4. 2-Hydroxy-2-carboxypentane-1,5-dioic acid (Citric acid)

[0111] HOOC CH₂ C (OH) (COOH) CH₂ COOH

[0112] 5. 2,3,4,5-Tetrahydroxyhexane-1,6-dioic acid (Isomers; saccharicacid, mucic acid etc.)

[0113] HOOC (CHOH)₄ COOH

[0114] (5) Lactone Forms

[0115] The typical lactone forms are gluconolactone, galactonolactone,glucuronolactone, galacturonolactone, gulonolactone, ribonolactone,saccharic acid lactone, pantoyllactone, glucoheptonolactone,mannonolactone, and galactoheptonolactone.

[0116] The second group of compounds which may be incorporated intoamphoteric or pseudoamphoteric compositions for cosmetic conditions anddermatologic disorders, is organic carboxylic acids in which the alphacarbon of the acids is in keto form. The generic structure of such alphaketoacids may be represented as follows:

(Ra) CO COO(Rb)

[0117] wherein Ra and Rb are H, alkyl, aralkyl or aryl group ofsaturated or unsaturated, isomeric or non-isomeric, straight or branchedchain or cyclic form, having 1 to 25 carbon atoms, and in addition Ramay carry F, Cl, Br, I, OH, CHO, COOH and alkoxy group having 1 to 9carbon atoms. The alpha ketoacids may be present as a free acid or anester form, or in a salt form with an organic base or an inorganicalkali. The typical alkyl, aralkyl and aryl groups for Ra and Rb includemethyl, ethyl, propyl, isopropyl, butyl, pentyl, octyl, lauryl, stearyl,benzyl and phenyl, etc.

[0118] In contrast to alpha hydroxyacids the ester form of alphaketoacids has been found to be therapeutically effective for cosmeticand dermatologic conditions and disorders. For example, while ethyllactate has a minimal effect, ethyl pyruvate is therapeutically veryeffective. Although the real mechanism for such difference is not known,we have speculated that the ester form of an alpha ketoacid ischemically and/or biochemically very reactive, and a free acid form ofthe alpha ketoacid is released in the skin after the topicalapplication.

[0119] The representative alpha ketoacids and their esters which may beuseful in amphoteric or pseudoamphoteric compositions for cosmeticconditions and dermatologic disorders are listed below:

[0120] 1. 2-Ketoethanoic acid (Glyoxylic acid)

[0121] (H) CO COOH

[0122] 2. Methyl 2-ketoethanoate

[0123] (H) CO COOCH₃

[0124] 3. 2-Ketopropanoic acid (Pyruvic acid)

[0125] CH₃ CO COOH

[0126] 4. Methyl 2-ketopropanoate (Methyl pyruvate)

[0127] CH₃ CO COOCH₃

[0128] 5. Ethyl 2-ketopropanoate (Ethyl pyruvate)

[0129] CH₃ CO COOC₂H₅

[0130] 6. Propyl 2-ketopropanoate (Propyl pyruvate)

[0131] CH₃ CO COOC₃H₇

[0132] 7. 2-Phenyl-2-ketoethanoic acid (Benzoylformic acid)

[0133] C₆H₅ CO COOH

[0134] 8. Methyl 2-phenyl-2-ketoethanoate (Methyl benzoylformate)

[0135] C₆H₅ CO COOCH₃

[0136] 9. Ethyl 2-phenyl-2-ketoethanoate (Ethyl benzoylformate)

[0137] C₆H₅ CO COOC₂H₅

[0138] 10. 3-Phenyl-2-ketopropanoic acid (Phenylpyruvic acid)

[0139] C₆H₅CH₂ CO COOH

[0140] 11. Methyl 3-phenyl-2-ketopropanoate (Methyl phenylpyruvate)

[0141] C₆H₅CH₂ CO COOCH₃

[0142] 12. Ethyl 3-phenyl-2-ketopropanoate (Ethyl phenylpyruvate)

[0143] C₆H₅CH₂ CO COOC₂H₅

[0144] 13. 2-Ketobutanoic acid

[0145] C₂H₅ CO COOH

[0146] 14. 2-Ketopentanoic acid

[0147] C₃H₇ CO COOH

[0148] 15. 2-Ketohexanoic acid

[0149] C₄H₉ CO COOH

[0150] 16. 2-Ketoheptanoic acid

[0151] C₅H₁₁ CO COOH

[0152] 17. 2-Ketooctanoic acid

[0153] C₆H₁₃ CO COOH

[0154] 18. 2-Ketododecanoic acid

[0155] C₁₀H₂₁ CO COOH

[0156] 19. Methyl 2-ketooctanoate

[0157] C₆H₁₃ CO COOCH₃

[0158] The third group of compounds which may be incorporated intoamphoteric or pseudoamphoteric compositions for cosmetic anddermatologic conditions and disorders, is chemically related to alphahydroxyacids or alpha ketoacids, and can be represented by their namesinstead of the above two generic structures. The third group ofcompounds include ascorbic acid, quinic acid, isocitric acid, tropicacid, trethocanic acid, 3-chlorolactic acid, cerebronic acid, citramalicacid, agaricic acid, 2-hydroxynervonic acid, aleuritic acid and pantoicacid.

II. Dimeric and Polymeric Forms of Hydroxyacids

[0159] When two or more molecules of hydroxycarboxylic acids eitheridentical or non-identical compounds are reacted chemically to eachother, dimeric or polymeric compounds will be formed. Such dimeric andpolymeric compounds may be classified into three groups, namely (a)acyclic ester, (b) cyclic ester and (c) miscellaneous dimer and polymer.

[0160] (a) Acyclic ester. The acyclic ester of a hydroxycarboxylic acidmay be a dimer or a polymer. The dimer is formed from two molecules of ahydroxycarboxylic acid by reacting the carboxyl group of one moleculewith the hydroxy group of a second molecule. For example, glycolylglycollate is formed from two molecules of glycolic acid by eliminatingone mole of water molecule. Likewise, lactyl lactate is formed from twomolecules of lactic acid. When two molecules of differenthydroxycarboxylic acids are intermolecularly reacted, a different dimeris formed. For example, glycolyl lactate is formed by reacting thecarboxyl group of lactic acid with the hydroxy group of glycolic acid.The polymer is formed in a similar manner but from more than twomolecules of a hydroxycarboxylic acid. For example, glycoly glycolyglycollate is formed from three molecules of glycolic acid. Copolymer isformed from two or more than two different kinds of hydroxycarboxylicacids. For example, glycolyl lactyl glycollate is formed from twomolecules of glycolic acid and one molecule of lactic acid.

[0161] The acyclic ester of dimeric and polymeric hydroxycarboxylicacids may be shown by the following chemical structure:

H [—O—C(Ra)(Rb)—CO—]n OH

[0162] wherein Ra,Rb=H, alkyl, aralkyl ar aryl group of saturated orunsaturated, isomeric or non-isomeric, straight or branched chain orcyclic form, having 1 to 25 carbon atoms, and n=1 or any numericalnumber, with a preferred number of up to 200. Ra and Rb in monomer unit2, 3, 4 and so on may be the same or the different groups from that inmonomer unit 1. For example, Ra,Rb=H in monomer unit 1, and Ra=CH₃,Rb=Hin monomer unit 2 when n=2 is a dimer called lactyl glycollate, becausethe first monomer is glycollate unit and the second monomer is lacticacid unit. The hydrogen atom in Ra and Rb may be substituted by ahalogen atom or a radical such as a lower alkyl, aralkyl, aryl or alkoxyof saturated or unsaturated, isomeric or non-isomeric, straight orbranched chain or cyclic form, having 1 to 9 carbon atoms. The dimer andpolymer of a hydroxycarboxylic acid may be present as a free acid, esteror salt form with organic base or inorganic alkali.

[0163] The typical alkyl, aralkyl and aryl groups for Ra and Rb includemethyl, ethyl, propyl, isopropyl, butyl, benzyl and phenyl.Representative acyclic esters of hydroxycarboxylic acids which may beuseful for cosmetic conditions and dermatologic disorders are listedbelow:

[0164] 1. Glycolyl glycollate (Glycolic acid glycollate)

[0165] Ra,Rb=H in units 1 & 2, n=2

[0166] 2. Lactyl lactate (Lactic acid lactate)

[0167] Ra=CH₃,Rb=H in units 1&2, n=2

[0168] 3. Mandelyl mandellate

[0169] Ra=C₆H₅,Rb=H in units 1 & 2, n=2

[0170] 4. Atrolactyl atrolactate

[0171] Ra=C₆H₅,Rb=CH₃ in units 1 & 2, n=2

[0172] 5. Phenyllactyl phenyllactate

[0173] Ra=C₆H₅CH₂, Rb=H, in units 1 & 2, n=2

[0174] 6. Benzilyl benzillate

[0175] Ra,Rb=C₆H₅ in units 1 & 2, n=2

[0176] 7. Glycolyl lactate

[0177] Ra=CH₃ in unit 1, Ra=H in unit 2, Rb=H in units 1 & 2, n=2

[0178] 8. Lactyl glycollate

[0179] Ra=H in unit 1, Ra=CH₃ in unit 2, Rb=H in units 1 & 2, n=2

[0180] 9. Glycolyl glycolyl glycollate

[0181] Ra,Rb=H in units 1, 2 & 3, n=3

[0182] 10. Lactyl lactyl lactate

[0183] Ra=CH₃, Rb=H in units 1, 2 & 3, n=3

[0184] 11. Lactyl glycolyl lactate

[0185] Ra=CH₃ in units 1 & 3, Ra=H in unit 2, Rb=H in units 1, 2 & 3,n=3

[0186] 12. Glycolyl glycolyl glycolyl glycollate

[0187] Ra,Rb=H in units 1, 2, 3 & 4, n=4

[0188] 13. Lactyl lactyl lactyl lactate

[0189] Ra=CH₃, Rb=H in units 1, 2, 3 & 4, n=4

[0190] 14. Glycolyl lactyl glycolyl lactyl glycollate

[0191] Ra=H in units 1, 3 & 5, Ra=CH₃ in units 2 & 4, Rb=H in units 1,2, 3, 4 & 5, n=5

[0192] 15. Polyglycolic acid and polylactic acid

[0193] (b) Cyclic ester. The cyclic ester of a hydroxycarboxylic acidmay also be a dimer or polymer, the most common type however, is a dimerform. The cyclic dimer may be formed from an identical monomer ordifferent monomers. For example, glycolide is formed from two moleculesof glycolic acid by removing two molecules of water, and lactide isformed from two molecules of lactic acid in the same manner. The cyclicester of dimeric and polymeric hydroxycarboxylic acids may be shown bythe following chemical structure:

[—O—C(Ra)(Rb)—Co—]n

[0194] wherein Ra,Rb=H, alkyl, aralkyl or aryl group of saturated orunsaturated, isomeric or non-isomeric, straight or branched chain orcyclic form, having 1 to 25 carbon atoms, and n=1 or any numericalnumber, however with a preferred number of 2. Ra and Rb in units 1, 2, 3and so on may be the same or the different groups. For example, inglycolide Ra and Rb are H in both units 1 & 2, but in lactoglycolide Rais H in unit 1, CH₃ in unit 2 and Rb is H in both units 1 & 2. Thehydrogen atom in Ra and Rb may be substituted by a halogen atom or aradical such as a lower alkyl, aralkyl, aryl or alkoxy of saturated orunsaturated, isomeric or non-isomeric, straight or branched chain orcyclic form, having 1 to 9 carbon atoms.

[0195] The typical alkyl, aralkyl and aryl groups for Ra and Rb includemethyl, ethyl, propyl, isopropyl, butyl, benzyl and phenyl.Representative cyclic esters of hydroxycarboxylic acids which may beuseful for cosmetic conditions and dermatologic disorders are listedbelow:

[0196] 1. Glycolide

[0197] Ra,Rb=H, n=2

[0198] 2. Lactide

[0199] Ra=CH₃, Rb=H in units 1 & 2, n=2

[0200] 3. Mandelide

[0201] Ra=C₆H₅, Rb=H in units 1 & 2, n=2

[0202] 4. Atrolactide

[0203] Ra=C₆H5, Rb=CH₃ in units 1 & 2, n=2

[0204] 5. Phenyllactide

[0205] Ra=C₆H₅ CH₂, Rb=H in units 1 & 2, n=2

[0206] 6. Benzilide

[0207] Ra,Rb=C₆H₅ in units 1 & 2, n=2

[0208] 7. Methyllactide

[0209] Ra,Rb=CH₃ in units 1 & 2, n=2

[0210] 8. Lactoglycolide

[0211] Ra=H in unit 1, Ra=CH₃ in unit 2

[0212] Rb=H in units 1 & 2, n=2

[0213] 9. Glycolactide

[0214] Ra=CH₃ in unit 1, Ra=H in unit 2

[0215] Rb=H in units 1 & 2, n=2

[0216] (c) Miscellaneous dimer and polymer. This group includes all thedimeric and polymeric forms of hydroxycarboxylic acids, which can not berepresented by any one of the above two generic structures, such asthose formed from tropic acid, trethocanic acid and aleuritic acid. Whena hydroxycarboxylic acid has more than one hydroxy or carboxy group inthe molecule a complex polymer may be formed. Such complex polymer mayconsist of acyclic as well as cyclic structures.

[0217] The following hydroxycarboxylic acids have more than one hydroxygroups: glyceric acid, gluconic acid and gluconolactone, galactonic acidand galactonolactone, glucuronic acid and glucuronolactone, ribonic acidand ribonolactone, galacturonic acid and galacturonolactone, ascorbicacid, gulonic acid and gulonolactone, glucoheptonic acid andglucoheptonolactone. These polyhydroxycarboxylic acids can form complexpolymers with themselves or with other simple monohydroxymonocarboxylicacids.

[0218] The following hydroxycarboxylic acids have more than one carboxylgroups: malic acid, citric acid, citramalic acid, tartronic acid,agaricic acid and isocitric acid. These monohydroxypolycarboxylic acidscan also form complex polymers with themselves or with other simplehydroxycarboxylic acids.

[0219] The following hydroxycarboxylic acids have more than one hydroxyand more than one carboxyl groups: tartaric acid, mucic acid andsaccharic acid. These polyhydroxypolycarboxylic acids can form even morecomplex polymers with themselves or with other hydroxycarboxylic acids.

III. Combination Compositions

[0220] Any cosmetic and pharmaceutical agents may be incorporated intoamphoteric or pseudoamphoteric compositions, or into compositionscontaining dimeric or polymeric forms of hydroxyacids with or withoutamphoteric or pseudoamphoteric systems to enhance therapeutic effects ofthose cosmetic and pharmaceutical agents to improve cosmetic conditionsor to alleviate the symptoms of dermatologic disorder. Cosmetic andpharmaceutical agents include those that improve or eradicate age spots,keratoses and wrinkles; analgesics; anesthetics; antiacne agents;antibacterials; antiyeast agents; antifungal agents; antiviral agents;antidandruff agents; antidermatitis agents; antipruritic agents;antiemetics; antimotion sickness agents; antiinflammatory agents;antihyperkeratolytic agents; antidryskin agents; antiperspirants;antipsoriatic agents; antiseborrheic agents; hair conditioners and hairtreatment agents; antiaging and antiwrinkle agents; antiasthmatic agentsand bronchodilators; sunscreen agents; antihistamine agents; skinlightening agents; depigmenting agents; vitamins; corticosteroids;tanning agents; hormones; retinoids; topical cardiovascular agents andother dermatologicals.

[0221] Some examples of cosmetic and pharmaceutical agents areclotrimazole, ketoconazole, miconazole, griseofulvin, hydroxyzine,diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine,monobenzone, erythromycin, tetracycline, clindamycin, meclocycline,hydroquinone, minocycline, naproxen, ibuprofen, theophylline, cromolyn,albuterol, retinoic acid, 13-cis retinoic acid, hydrocortisone,hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone17-butyrate, betamethasone valerate, betamethasone dipropionate,triamcinolone acetonide, fluocinonide, clobetasol propionate, benzoylperoxide, crotamiton, propranolol, promethazine, vitamin A palmitate andvitamin E acetate.

IV. Specific Compositions For Skin Disorders

[0222] We have discovered that topical formulations or compositionscontaining specific alpha hydroxyacids or alpha ketoacids, or relatedcompounds are therapeutically very effective for certain skin disorderswithout utilizing any amphoteric or pseudoamphoteric systems. The alphahydroxyacids and the related compounds include 2-hydroxyethanoic acid,2-hydroxypropanoic acid, 2-methyl 2-hydroxypropanoic acid, 2-phenyl2-hydroxyethanoic acid, 2,2-diphenyl 2-hydroxyethanoic acid, 2-phenyl2-methyl 2-hydroxyethanoic acid and 2-phenyl 3-hydroxypropanoic acid.The alpha ketoacids and their esters include 2-ketopropanoic acid,methyl 2-ketopropanoate and ethyl 2-ketopropanoate. The mentioned skindisorders include warts, keratoses, age spots, acne, nail infections,wrinkles and aging related skin changes.

[0223] In general, the concentration of the alpha hydroxyacid, the alphaketoacid or the related compound used in the composition is a fullstrength to an intermediate strength, therefore the dispensing and theapplication require special handling and procedures.

[0224] If the alpha hdyroxyacid, or the alpha ketoacid or the relatedcompound at full strength (usually 95-100%) is a liquid form at roomtemperature such as 2-hydroxypropanoic acid, 2-ketopropanoic acid,methyl 2-ketopropanoate and ethyl 2-ketopropanoate, the liquid compoundwith or without a gelling agent is directly dispensed as 0.5 to 1 mlaliquots in small vials.

[0225] If the alpha hydroxyacid, or the alpha ketoacid or the relatedcompound at full strength is a solid form at room temperature such as2-hydroxyethanoic acid, 2-methyl 2-hydroxypropanoic acid, 2-phenyl2-hydroxyethanoic acid, 2,2-diphenyl 2-hydroxyethanoic acid and 2-phenyl3-hydroxypropanoic acid, the solid compound is first dissolved in aminimal amount of vehicle or vehicle system such as water, or ethanoland propylene glycol with or without a gelling agent. For example,2-hydroxyethanoic acid 70 g is dissolved in water 30 g, and the 70%strength solution thus obtained is dispensed as 0.5 to 1 ml aliquots insmall vials. If a gelling agent is used, 0.5 to 3% of for example,hydroxyethyl cellulose, methyl cellulose, hydroxypropyl cellulose orcarbomer may be incorporated into the above solution.

[0226] To prepare an intermediate strength (usually 20-50%), the alphahydroxyacid, alpha ketoacid or related compound either a liquid or solidform at room temperature is first dissolved in a vehicle or vehiclesystem such as water, acetone, ethanol, propylene glycol and butane1,3-diol. For example, 2-hydroxyethanoic acid or 2-ketopropanoic acid 30g is dissolved in ethanol 56 g and propylene glycol 14 g, and the 30%strength solution thus obtained is dispensed as 7 to 14 ml aliquots indropper bottles.

[0227] For topical treatment of warts, keratoses, age spots, acne, nailinfections, wrinkles or aging related skin changes, patients are advisedto apply a small drop of the medication with a toothpick or afine-caliber, commonly available artist's camel hair brush to affectedlesions only and not surrounding skin. Prescribed applications have been1 to 6 times daily for keratoses and ordinary warts of the hands,fingers, palms, and soles. For age spots, acne, nail infections,wrinkles and aging related skin changes topical applications have been 1to 2 times daily.

[0228] Very often, frequency and duration of applications have beenmodified according to clinical responses and reactions of the lesionsand the patient or responsible family member is instructed accordingly.For example, some clinical manifestations other than pain have been usedas a signal to interrupt application. These manifestations includedistinct blanching of the lesions or distinct peripheral erythema.

[0229] Alternatively, an office procedure may be adapted when a fullstrength of 2-ketopropanoic acid or 70% 2-hydroxyethanoic acid is usedfor topical treatment of age spots, keratoses, acne, warts or facialwrinkles.

[0230] We have found that the above mentioned alpha hydroxyacids, alphaketoacids and related compounds are therapeutically effective fortopical treatments of warts, keratoses, age spots, acne, nailinfections, wrinkles and aging related skin changes.

Preparation of the Therapeutic Compositions

[0231] Amphoteric and pseudoamphoteric compositions of the instantinvention may be formulated as solution, gel, lotion, cream, ointment,shampoo, spray, stick, powder or other cosmetic and pharmaceuticalpreparations.

[0232] To prepare an amphoteric or pseudoamphoteric composition insolution form at least one of the aforementioned amphoteric orpseudoamphoteric compounds and in combination at least one of thehydroxyacids or the related compounds are dissolved in a solution whichmay consist of ethanol, water, propylene glycol, acetone or otherpharmaceutically acceptable vehicle. The concentration of the amphotericor pseudoamphoteric compound may range from 0.01 to 10 M, the preferredconcentration ranges from 0.1 to 3 M. The concentration of hydroxyacidsor the related compounds may range from 0.02 to 12 M, the preferredconcentration ranges from 0.2 to 5 M.

[0233] In the preparation of an amphoteric or pseudoamphotericcomposition in lotion, cream or ointment form, at least one of theamphoteric or pseudoamphoteric compounds and one of the hydroxyacids orthe related compounds are initially dissolved in a solvent such aswater, ethanol and/or propylene glycol. The solution thus prepared isthen mixed in a conventional manner with commonly available cream orointment base such as hydrophilic ointment or petrolatum. Theconcentrations of amphoteric or pseudoamphoteric compounds andhydroxyacids used in the compositions are the same as described above.

[0234] Amphoteric and pseudoamphoteric compositions of the instantinvention may also be formulated in a gel form. A typical gelcomposition of the instant invention utilizes at least one of theamphoteric or pseudoamphoteric compounds and one of the hydroxyacids orthe related compounds are dissolved in a mixture of ethanol, water andpropylene glycol in a volume ratio of 40:40:20, respectively. A gellingagent such as methyl cellulose, ethyl cellulose, hydroxyethylcellulose,hydroxypropylcellulose, hydroxypropylmethylcellulose, carbomer orammoniated glycyrrhizinate is then added to the mixture with agitation.The preferred concentration of the gelling agent may range from 0.1 to 4percent by weight of the total composition.

[0235] Since dimeric and polymeric forms of hydroxyacids are less stablein the presence of water or the like vehicle, cosmetic andpharmaceutical compositions should be prepared as anhydrousformulations. Typical vehicles suitable for such formulations includemineral oil, petrolatum, isopropyl myristate, isopropyl palmitate,diisopropyl adipate, occtyl palmitate, acetone, squalene, squalane,silicone oils, vegetable oils and the like. Therapeutic compositionscontaining dimeric or polymeric forms of hydroxyacids do not require anyincorporation of an amphoteric or pseudoamphoteric compound. Theconcentration of the dimeric or polymeric form of a hydroxyacid used inthe composition may range from 0.1 to 100%, the preferred concentrationranges from 1 to 40%. Therapeutic compositions may be formulated asanhydrous solution, lotion, ointment, spray, powder or the like.

[0236] To prepare a combination composition in a pharmaceuticallyacceptable vehicle, a cosmetic or pharmaceutical agent is incorporatedinto any one of the above composition by dissolving or mixing the agentinto the formulation.

[0237] The following are illustrative examples of formulations andcompositions according to this invention. Although the examples utilizeonly selected compounds and formulations, it should be understood thatthe following examples are illustrative and not limited. therefore, anyof the aforementioned amphoteric or pseudoamphoteric compounds,hydroxyacids, dimeric or polymeric forms of hydroxyacids may besubstituted according to the teachings of this invention in thefollowing examples.

EXAMPLE 1

[0238] An amphoteric composition containing 1 M 2-hydroxyethanoic acidand 0.5 M L-arginine in solution form for dandruff or dry skin may beformulated as follows.

[0239] 2-Hydroxyethanoic acid (glycolic acid) 7.6 g is dissolved inwater 60 ml and propylene glycol 20 ml. L-Arginine 8.7 g is added to thesolution with stirring until all the crystals are dissolved. Ethanol isadded to make a total volume of the solution to 100 ml. The amphotericcomposition thus formulated has pH 3.0. An amphoteric compositionformulated from 1 M 2-hydroxyethanoic acid and 1 M L-arginine has pH6.3. The solution has pH 1.9 if no amphoteric compound is incorporated.

EXAMPLE 2

[0240] An amphoteric composition containing 1 M 2-hydroxyethanoic acidand 0.5 M L-lysine in a cream form for dry skin and other dermatologicand cosmetic conditions may be formulated as follows.

[0241] 2-Hydroxyethanoic acid 7.6 g and L-lysine 7.3 g are dissolved in30 ml of water, and the solution thus obtained is mixed with sufficientamount of an oil-in-water emulsion to make a total volume of 100 ml. Theamphoteric composition thus formulated has pH 3.3.

EXAMPLE 3

[0242] An amphoteric composition containing 1 M 2-hydroxyethanoic acidand 0.5 M 4-aminobutanoic acid in lotion form for cosmetic anddermatologic conditions may be formulated as follows.

[0243] 2-Hydroxyethanoic acid 7.6 g and 4-aminobutanoic acid 5.2 g aredissolved in water 30 ml, and the solution is mixed with 50 g of anoil-in-water emulsion. The lotion thus obtained is made up to 100 ml involume with more oil-in-water emulsion. The amphoteric composition thusformulated has pH 3.1.

EXAMPLE 4

[0244] A pseudoamphoteric composition containing 1 M 2-hydroxyethanoicacid and 0.5 M creatinine in solution form for cosmetic conditions anddermatologic disorders may be formulated as follows.

[0245] 2-Hydroxyethanoic acid 7.6 g is dissolved in water 70 ml andpropylene glycol 10 ml. Creatinine 5.7 g is added to the solution withstirring until all the crystals are dissolved. More water is added tomake a total volume of the solution to 100 ml. The pseudoamphotericcomposition thus formulated has pH 3.2. The composition has pH 4.0 when1 M instead of 0.5 M creatinine is incorporated into the formulation.

EXAMPLE 5

[0246] An amphoteric composition containing 1 M 2-hydroxyethanoic acidand 0.5 M L-histidine in a cream form for dermatologic and cosmeticconditions may be formulated as follows.

[0247] 2-Hydroxyethanoic acid 7.6 g and L-histidine 7.8 g are dissolvedin 25 ml of water, and the solution thus obtained is mixed withsufficient amount of an oil-in-water emulsion to make a total volume of100 ml. The amphoteric composition thus formulated has pH 3.2.

EXAMPLE 6

[0248] An amphoteric composition containing 0.5 M 2-hydroxyethanoic acidand 0.5 M dipeptide of β-Ala-L-His for cosmetic and dermatologicconditions may be formulated as follows.

[0249] 2-Hydroxyethanoic acid 3.8 g and L-carnosine(β-alanyl-L-histidine) 11.3 g are dissolved in water 40 ml and propyleneglycol 20 ml. After all the crystals have been dissolved sufficientamount of ethanol is added to make a total volume of the solution to 100ml. The amphoteric composition thus formulated has pH 4.5.

EXAMPLE 7

[0250] An amphoteric composition containing 0.5 M 2-hydroxyethanoic acidand 0.5 M cycloleucine for cosmetic and dermatologic conditions may beformulated as follows.

[0251] 2-Hydroxyethanoic acid 3.8 g and 1-aminocyclopentane-1-carboxylicacid (cycloleucine) 6.5 g are dissolved in water 40 ml and propyleneglycol 20 ml. After all the crystals have been dissolved sufficientamount of ethanol is added to make a total volume of the solution to 100ml. The amphoteric composition thus formulated has pH 3.2.

EXAMPLE 8

[0252] A pseudoamphoteric composition containing 0.5 M 2-hydroxyethanoicacid and 0.25 M 1,12-diaminododecane for cosmetic and dermatologicconditions may be formulated as follows.

[0253] 2-Hydroxyethanoic acid 3.8 g and 1.12-diaminododecane 5 g aredissolved in water 40 ml and propylene glycol 20 ml. After all thecrystals have been dissolved sufficient amount of ethanol is added tomake a total volume of the solution to 100 ml. The pseudoamphotericcomposition thus formulated has pH 4.2.

EXAMPLE 9

[0254] An amphoteric composition containing 0.5 M 2-hydroxyethanoic acidand 5% protamine for cosmetic and dermatologic conditions may beformulated as follows.

[0255] 2-Hydroxyethanoic acid 3.8 g and protamine 5 g, isolated andpurified from salmon sperm are dissolved in water 25 ml. The solutionthus obtained is mixed with sufficient amount of an oil-in-wateremulsion to make a total volume of 100 ml. The amphoteric compositionthus formulated has pH 3.2.

EXAMPLE 10

[0256] An amphoteric composition containing 1 M 2-hydroxypropanoic acidand 0.5 M L-arginine in solution form for dandruff or dry skin may beformulated as follows.

[0257] 2-Hydroxypropanoic acid (DL-lactic acid) USP grade 9.0 g isdissolved in water 60 ml and propylene glycol 20 ml. L-Arginine 8.7 g isadded to the solution with stirring until all the crystals aredissolved. Ethanol is added to make a total volume of the solution to100 ml. The amphoteric composition thus formulated has pH 3.1. Anamphoteric composition formulated from 1 M 2-hydroxypropanoic acid and 1M L-arginine has pH 6.9. The solution has pH 1.9 if no amphotericcompound is incorporated.

EXAMPLE 11

[0258] An amphoteric composition containing 1 M 2-hydroxypropanoic acidand 0.5 M L-lysine in a cream form for dry skin and other dermatologicand cosmetic conditions may be formulated as follows.

[0259] 2-Hydroxypropanoic acid 9.0 g and L-lysine 7.3 g are dissolved in30 ml of water, and the solution thus obtained is mixed with sufficientamount of an oil-in-water emulsion to make a total volume of 100 ml. Theamphoteric composition thus formulated has pH 3.6. An amphotericcomposition formulated from 1 M 2-hydroxypropanoic acid and 1 M L-lysinehas pH 8.4

EXAMPLE 12

[0260] An amphoteric composition containing 1 M 2-hydroxypropanoic acidand 0.5 M 4-aminobutanoic acid in lotion form for cosmetic anddermatologic conditions may be formulated as follows.

[0261] 2-Hydroxypropanoic acid 9.0 g and 4-aminobutanoic acid 5.2 g aredissolved in water 30 ml, and the solution is mixed with 50 g of anoil-in-water emulsion. The lotion thus obtained is made up to 100 ml involume with more oil-in-water emulsion. The amphoteric composition thusformulated has pH 3.0

EXAMPLE 13

[0262] A pseudoamphoteric composition containing 1 M 2-hydroxypropanoicacid and 0.5 M creatinine in solution form for cosmetic conditions anddermatologic disorders may be formulated as follows.

[0263] 2-Hydroxypropanoic acid 9.0 g is dissolved in water 70 ml andpropylene glycol 10 ml. Creatinine 5.7 g is added to the solution withstirring until all the crystals are dissolved. More water is added tomake a total volume of the solution to 100 ml. The pseudoamphotericcomposition thus formulated has pH 3.3. The composition has pH 4.4 when1 M instead of 0.5 M creatinine is incorporated into the formulation.

EXAMPLE 14

[0264] An amphoteric composition containing 1 M 2-hydroxypropanoic acidand 1 M L-histidine in a cream form for dermatologic and cosmeticconditions may be formulated as follows.

[0265] 2-Hydroxypropanoic acid 9.0 g and L-histidine 15.5 g aredissolved in 35 ml of water, and the solution thus obtained is mixedwith sufficient amount of an oil-in-water emulsion to make a totalvolume of 100 ml. The amphoteric composition thus formulated as pH 4.9.

EXAMPLE 15

[0266] An amphoteric composition containing 1 M 2-hydroxypropanoic acidand 1 M dipeptide of Gly-Gly for cosmetic and dermatologic conditionsmay be formulated as follows.

[0267] 2-Hydroxypropanoic acid 9.0 g and glycylglycine 13.2 g aredissolved in water 40 ml and propylene glycol 20 ml. After all thecrystals have been dissolved sufficient amount of ethanol is added tomake a total volume of the solution to 100 ml. The amphotericcomposition thus formulated has pH 3.0.

EXAMPLE 16

[0268] An amphoteric composition containing 1 M2-methyl-2-hydroxypropanoic acid and 0.5 M L-arginine in solution formfor dandruff or dry skin may be formulated as follows.

[0269] 2-Methyl-2-hydroxypropanoic acid (methyllactic acid) 10.4 g isdissolved in water 60 ml and propylene glycol 20 ml. L-Arginine 8.7 g isadded to the solution with stirring until all the crystals aredissolved. Ethanol is added to make a total volume of the solution to100 ml. The amphoteric composition thus formulated has pH 3.3. Anamphoteric composition formulated from 1 M 2-methyl-2-hydroxypropanoicacid and 1 M L-arginine has pH 6.5. The solution has pH 1.9 if noamphoteric compound is incorporated.

EXAMPLE 17

[0270] An amphoteric composition containing 1 M2-methyl-2-hydroxypropanoic acid and 0.5 M 4-aminobutanoic acid in acream form for dry skin and other dermatologic and cosmetic conditionsmay be formulated as follows.

[0271] 2-Methyl-2-hydroxypropanoic acid 10.4 g and 4-aminobutanoic acid5.2 g are dissolved in 30 ml of water, and the solution thus obtained ismixed with sufficient amount of an oil-in-water emulsion to make a totalvolume of 100 ml. The amphoteric composition thus formulated has pH 3.2.

EXAMPLE 18

[0272] An amphoteric composition containing 1 M2-methyl-2-hydroxypropanoic acid and 1 M dipeptide of Gly-Gly in lotionform for cosmetic and dermatologic conditions may be formulated asfollows.

[0273] 2-Methyl-2-hydroxypropanoic acid 10.4 g and glycylglycine 13.2 gare dissolved in water 30 ml, and the solution is mixed with 50 g of anoil-in-water emulsion. The lotion thus obtained is made up to 100 ml involume with more oil-in-water emulsion. The amphoteric composition thusformulated has pH 3.0.

EXAMPLE 19

[0274] A pseudoamphoteric composition containing 1 M2-methyl-2-hydroxypropanoic acid and 0.5 M creatinine in solution formfor cosmetic conditions and dermatologic disorders may be formulated asfollows.

[0275] 2-Methyl-2-hydroxypropanoic acid 10.4 g is dissolved in water 70ml and propylene glycol 10 ml. Creatinine 5.7 g is added to the solutionwith stirring until all the crystals are dissolved. More water is addedto make a total volume of the solution to 100 ml. The pseudoamphotericcomposition thus formulated has pH 3.4. The composition has pH 4.4 when1 M instead of 0.5 M creatinine is incorporated into the formulation.

EXAMPLE 20

[0276] An amphoteric composition containing 0.5 M2-phenyl-2-hydroxyethanoic acid and 0.5 M L-histidine in a cream formfor dermatologic and cosmetic conditions may be formulated as follows.

[0277] 2-Phenyl 2-hydroxyethanoic acid (mandelic acid) 7.6 g andL-histidine 7.8 g are dissolved in 25 ml of water, and the solution thusobtained is mixed with sufficient amount of an oil-in-water emulsion tomake a total volume of 100 ml. The amphoteric composition thusformulated has pH 5.0. The composition has pH 2.2 if no amphotericcompound is incorporated.

EXAMPLE 21

[0278] An amphoteric composition containing 0.5 M2-phenyl-2-hydroxyethanoic acid and 0.5 M L-lysine for cosmetic anddermatologic conditions may be formulated as follows.

[0279] 2-Phenyl 2-hydroxyethanoic acid 7.6 g and L-lysine 7.3 g aredissolved in 25 ml of water. The solution thus obtained is mixed with anoil-in-water emulsion to make a total volume of 100 ml. The amphotericcomposition thus formulated for pH 4.6.

EXAMPLE 22

[0280] A pseudoamphoteric composition containing 0.5 M 2-phenyl2-hydroxyethanoic acid and 0.5 M creatinine for cosmetic anddermatologic conditions may be formulated as follows.

[0281] 2-Phenyl 2-hydroxyethanoic acid 7.6 g and creatinine 5.7 g aredissolved in 30 ml of water, and the solution thus obtained is mixedwith sufficient amount of an oil-in-water emulsion to make a totalvolume of 100 ml. The amphoteric composition thus formulated has pH 4.6.

EXAMPLE 23

[0282] An amphoteric composition containing 0.5 M 2-phenyl2-hydroxyethanoic acid and 0.5 M L-citrulline for cosmetic anddermatologic conditions may be formulated as follows.

[0283] 2-Phenyl 2-hydroxyethanoic acid 7.6 g and L-citrulline 8.8 g aredissolved in water 30 ml, and the solution is mixed with 50 g of anoil-in-water emulsion. The lotion thus obtained is made up to 100 ml involume with more oil-in-water emulsion. The amphoteric composition thusformulated has pH 3.0.

EXAMPLE 24

[0284] An amphoteric composition containing 1 M citric acid and 1 ML-arginine for cosmetic conditions and dermatologic disorders may beformulated as follows.

[0285] Citric acid 19.2 g is dissolved in water 50 ml and propyleneglycol 10 ml. L-Arginine 17.4 g is added to the solution with stirringuntil all the crystals are dissolved. More water is added to make atotal volume of the solution to 100 ml. The amphoteric composition thusformulated has pH 3.0. The composition has pH 1.8 if no amphotericcompound is incorporated.

EXAMPLE 25

[0286] A pseudoamphoteric composition containing 1 M citric acid and 1 Mcreatinine for dermatologic and cosmetic conditions may be formulated asfollows.

[0287] Citric acid 19.2 g and creatinine 11.3 g are dissolved in 40 mlof water, and the solution thus obtained is mixed with sufficient amountof an oil-in-water emulsion to make a total volume of 100 ml. Theamphoteric composition thus formulated has pH 3.7.

EXAMPLE 26

[0288] An amphoteric composition containing 1 M malic acid and 1 ML-arginine for cosmetic and dermatologic conditions may be formulated asfollows.

[0289] 2-Hydroxybutanedioic acid (DL-malic acid) 13.4 g and L-arginine17.4 g are dissolved in water 40 ml and propylene glycol 20 ml. Afterall the crystals have been dissolved sufficient amount of water is addedto make a total volume of the solution to 100 ml. The amphotericcomposition thus formulated has pH 3.3. The composition has pH 1.8 if noamphoteric compound is incorporated.

EXAMPLE 27

[0290] A pseudoamphoteric composition containing 1 M malic acid and 0.5M creatinine for cosmetic and dermatologic conditions may be formulatedas follows.

[0291] DL-Malic acid 13.4 g and creatinine 5.7 g are dissolved in water40 ml and propylene glycol 20 ml. After all the crystals have beendissolved sufficient amount of water is added to make a total volume ofthe solution to 100 ml. The pseudoamphoteric composition thus formulatedhas pH 3.0. The composition has pH 3.8 when 1 M instead of 0.5 Mcreatinine is incorporated into the formulation.

EXAMPLE 28

[0292] An amphoteric composition containing 1 M tartaric acid and 1 ML-arginine for cosmetic and dermatologic conditions may be formulated asfollows.

[0293] 2,3-Dihydroxybutanedioic acid (DL-tartaric acid) 15.9 g andL-arginine 17.4 g are dissolved in water 40 ml and propylene glycol 20ml. After all the crystals have been dissolved sufficient amount ofwater is added to make a total volume of the solution to 100 ml. Theamphoteric composition thus formulated has pH 3.0. The composition haspH 1.7 if no amphoteric compound is incorporated.

EXAMPLE 29

[0294] A pseudoamphoteric composition containing 1 M tartaric acid and 1M creatinine for cosmetic and dermatologic conditions may be formulatedas follows.

[0295] DL-Tartaric acid 15.0 g and creatinine 11.3 g are dissolved in 35ml of water. The solution thus obtained is mixed with sufficient amountof an oil-in-water emulsion to make a total volume of 100 ml. Thepseudoamphoteric composition thus formulated has pH 3.4.

EXAMPLE 30

[0296] An amphoteric composition containing 1 M gluconolactone and 0.5 ML-arginine for cosmetic and dermatologic conditions may be formulated asfollows.

[0297] Gluconolactone 17.8 g and L-arginine 8.7 g are dissolved in water60 ml and propylene glycol 10 ml. After all the crystals have beendissolved sufficient water is added to make a total volume of thesolution to 100 ml. The amphoteric composition thus formulated has pH3.1. The composition has pH 5.9 when 1 M instead of 0.5 M L-arginine isincorporated into the formulation. If no amphoteric compound isincorporated the pH of the composition is 1.8.

EXAMPLE 31

[0298] An amphoteric composition containing 1 M gluconolactone and 0.5 M4-aminobutanoic acid for cosmetic and dermatologic conditions may beformulated as follows.

[0299] Gluconolactone 17.8 g and 4-aminobutanoic acid 5.2 g aredissolved in water 60 ml and propylene glycol 10 ml. After all thecrystals ave been dissolved sufficient water is added to make a totalvolume of the solution to 100 ml. The amphoteric composition thusformulated has pH 3.2.

EXAMPLE 32

[0300] An amphoteric composition containing 1 M gluconolactone and 1 Mdipeptide of Gly-Gly for cosmetic and dermatologic conditions may beformulated as follows.

[0301] Gluconolactone 17.8 g and glycylglycine 13.2 g are dissolved inwater 50 ml and propylene glycol 5 ml. More water is added to make atotal volume of the solution to 100 ml. The amphoteric composition thusformulated has pH 3.1

EXAMPLE 33

[0302] A pseudoamphoteric composition containing 1 M gluconolactone and0.5 M creatinine for cosmetic conditions and dermatologic disorders maybe formulated as follows.

[0303] Gluconolactone 17.8 g and creatinine 5.7 g are dissolved in water60 ml and propylene glycol 10 ml. More water is added to make a totalvolume of the solution to 100 ml. The pseudoamphoteric composition thusformulated has pH 3.2. The composition has pH 4.8 when 1 M instead of0.5 M creatinine is incorporated into the formulation.

EXAMPLE 34

[0304] A pseudoamphoteric composition containing 1 M pyruvic acid and 1M creatinine for dermatologic and cosmetic conditions may be formulatedas follows.

[0305] 2-Ketopropanoic acid (pyruvic acid) 8.8 g and creatinine 11.3 gare dissolved in water 25 ml. The solution thus obtained is mixed withsufficient amount of an oil-in-water emulsion to make a total volume of100 ml. The amphoteric composition thus formulated has pH 3.4.

EXAMPLE 35

[0306] An amphoteric composition containing 0.5 M benzilic acid and 0.5M L-lysine for cosmetic and dermatolqgic conditions may be formulated asfollows.

[0307] 2,2-Diphenyl 2-hydroxyethanoic acid (benzilic acid) 11.4 g andL-lysine 7.3 g are dissolved in water 40 ml and propylene glycol 20 ml.After all the crystals have been dissolved sufficient amount of ethanolis added to make a total volume of the solution to 100 ml. Theamphoteric composition thus formulated has pH 4.9. The composition haspH 2.7 if no amphoteric compound is incorporated.

EXAMPLE 36

[0308] An amphoteric composition containing 0.5 M benzilic acid and 0.5M L-histidine for cosmetic and dermatologic conditions may be formulatedas follows.

[0309] Benzilic acid 11.4 g and L-histidine 7.8 g are dissolved in water40 ml and propylene glycol 20 ml. Ethyl cellulose 2 g is added withstirring, and sufficient amount of ethanol is added to make a totalvolume of the gel to 100 ml. The amphoteric gel composition thusformulated has pH 5.0.

EXAMPLE 37

[0310] A pseudoamphoteric composition containing 0.5 M benzilic acid and0.5 M creatinine for cosmetic and dermatologic conditions may beformulated as follows.

[0311] Benzilic acid 11.4 g and creatinine 5.7 g are dissolved in water40 ml and propylene glycol 20 ml. Sufficient amount of ethanol is addedto make a total volume of the solution to 100 ml. The amphotericcomposition thus formulated has pH 4.9.

EXAMPLE 38

[0312] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 0.05% betamethasone dipropionate in a creamform for dermatologic disorders may be formulated as follows.

[0313] 2-Hydroxyethanoic acid 3.8 g and creatinine 5.7 g are dissolvedin 25 ml of water, and the solution thus obtained is mixed with 50 g ofan oil-in-water emulsion. Betamethasone dipropionate 1% in ethanolsolution 5 ml is added to the above mixture. More oil-in-water emulsionis added to make a total volume of 100 ml. The pseudoamphotericcomposition thus formulated has pH 4.2.

EXAMPLE 39

[0314] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 0.05% clobetasol propionate in a cream formfor dermatologic disorders may be formulated as follows.

[0315] 2-Hydroxyethanoic acid 3.8 g and creatinine 5.7 g are dissolvedin 25 ml of water, and the solution thus obtained is mixed with 50 g ofan oil-in-water emulsion. Clobetasol propionate 1% in acetone solution 5ml is added to the above mixtures. More oil-in-water emulsion is addedto make a total volume of 100 ml. The pseudoamphoteric composition thusformulated has pH 4.2.

EXAMPLE 40

[0316] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 0.1% triamcinolone acetonide in a cream formfor dermatologic disorders may be formulated as follows.

[0317] 2-Hydroxyethanoic acid 3.8 g and creatinine 5.7 g are dissolvedin 25 ml of water, and the solution thus obtained is mixed with 50 g ofan oil-in-water emulsion. Triamcinolone acetonide 2% solution ofacetone:ethanol (50:50), 5 ml is added to the above mixture. Moreoil-in-water emulsion is added to make a total volume of 100 ml. Thepseudoamphoteric composition thus formulated has pH 4.2.

EXAMPLE 41

[0318] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 0.2% 5-fluorouracil in a cream form fordermatologic disorders may be formulated as follows.

[0319] 2-Hydroxyethanoic acid 3.8 g and creatinine 5.7 g are dissolvedin 20 ml of water, and the solution thus obtained is mixed with 50 g ofan oil-in-water emulsion. 5-Fluorouracil 2% solution of propyleneglycol:water (95:5), 10 ml is added to the above mixture. Moreoil-in-water emulsion is added to make a total volume of 100 ml. Thepseudoamphoteric composition thus formulated has pH 4.1.

EXAMPLE 42

[0320] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxypropanoic acid and 0.05% betamethasone dipropionate in a creamform for dermatologic disorders may be formulated as follows.

[0321] 2-Hydroxypropanoic acid 4.5 g and creatinine 5.7 g are dissolvedin 25 ml of water, and the solution thus obtained is mixed with 50 g ofa oil-in-water emulsion. Betamethasone dipropionate 1% in ethanolsolution 5 ml is added to the above mixture. More oil-in-water emulsionis added to make a total volume of 100 ml. The pseudoamphotericcomposition thus formulated has pH 4.1.

EXAMPLE 43

[0322] A pseudoamphoteric composition containing in combination 0.5 Mhydroxypropanoic acid and 0.05% clobetasol propionate in a cream formfor dermatologic disorders may be formulated as follows.

[0323] 2-Hydroxypropanoic acid 4.5 g and creatinine 5.7 g are dissolvedin 25 ml of water, and the solution thus obtained is mixed with 50 g ofan oil-in-water emulsion. Clobetasol propionate 1% in acetone solution 5ml is added to the above mixture. More oil-in-water emulsion is added tomake a total volume of 100 ml. The pseudoamphoteric composition thusformulated has pH 4.1.

EXAMPLE 44

[0324] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxypropanoic acid and 0.1% triamcinolone acetonide in a cream formfor dermatologic disorders may be formulated as follows.

[0325] 2-Hydroxypropanoic acid 4.5 g and creatinine 5.7 g are dissolvedin 25 ml of water, and the solution thus obtained is mixed with 50 g ofan oil-in-water emulsion. Triamcinolone acetonide 2% solution ofacetone:ethanol (50:50), 5 ml is added to the above mixture. Moreoil-in-water emulsion is added to make a total volume of 100 ml. Thepseudoamphoteric composition thus formulated has pH 4.1.

EXAMPLE 45

[0326] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxypropanoic acid and 0.2% 5-fluorouracil in a cream form fordermatologic disorders may be formulated as follows.

[0327] 2-Hydroxypropanoic acid 4.5 g and creatinine 5.7 g are dissolvedin 20 ml of water, and the solution thus obtained is mixed with 50 g ofan oil-in-water emulsion. 5-Fluorouracil 2% solution of propyleneglycol:water (95:5), 10 ml is added to the above mixture. Moreoil-in-water emulsion is added to make a total volume of 100 ml. Thepseudoamphoteric composition thus formulated has pH 4.1.

EXAMPLE 46

[0328] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 2% clotrimazole in a cream form for athlete'sfoot and other fungal infections may be formulated as follows.

[0329] 2-Hydroxyethanoic acid 3.8 g, clotimazole 2 g and creatinine 5.7g are dissolved in water 20 ml and propylene glycol 5 ml, and thesolution thus obtained is mixed with enough amount of an oil-in-wateremulsion to make a total volume of 100 ml. The pseudoamphotericcomposition thus formulated has pH 4.2.

EXAMPLE 47

[0330] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 2% erythromycin in solution form for acne maybe formulated as follows.

[0331] 2-Hydroxyethanoic acid 3.8 g, erythromycin 2 g and creatinine 5.7g are dissolved in water 25 ml, ethanol 40 ml and propylene glycol 15ml. More water is then added to make a total volume of 100 ml. Thepseudoamphoteric composition thus formulated has pH 4.2.

EXAMPLE 48

[0332] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 1% ketoconazole in a cream form for fungalinfections may be formulated as follows.

[0333] 2-Hydroxyethanoic acid 3.8 g, ketoconazole 1 g and creatinine 5.7g are dissolved in 25 ml of water, and the solution thus obtained ismixed with enough amount of an oil-in-water emulsion to make a totalvolume of 100 ml. The pseudoamphoteric composition thus formulated haspH 4.2.

EXAMPLE 49

[0334] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxypropanoic acid and 2% clotrimazole in a cream form for fungalinfections may be formulated as follows.

[0335] 2-Hydroxypropanoic acid 3.8 g, clotrimazole 2 g and creatinine5.7 g are dissolved in 25 ml of water, and the solution thus obtained ismixed with enough amount of an oil-in-water emulsion to make a totalvolume of 100 ml. The pseudoamphoteric composition thus formulated haspH 4.1.

EXAMPLE 50

[0336] A pseudoamphoteric composition containing in combination 0.5 M2-hydroxyethanoic acid and 2% tetracycline in a gel form fordermatologic disorders may be formulated as follows.

[0337] 2-Hydroxyethanoic acid 3.8 g, tetracycline 2 g, creatinine 5.7 g,xantham gum 0.2 g, carbomer-941 1 g, propylene glycol 5 ml, ethanol 20ml and enough amount of water are homogenized to make a total volume of100 ml. The pseudoamphoteric composition thus formulated for acne andoily skin has pH 4.2.

EXAMPLE 51

[0338] An amphoteric composition containing 0.2 M aleuritic acid and 0.1M L-lysine in a solution form for cosmetic and dermatologic conditionsmay be formulated as follows.

[0339] Aleuritic acid 6.1 g and L-lysine 1.5 g are dissolved insufficient amount of a solution from ethanol:propylene glycol 80:20 tomake a total volume of 100 ml. The amphoteric composition thusformulated has pH 6.4.

EXAMPLE 52

[0340] A typical composition containing a dimeric form of alphahydroxyacid in solution for acne, dandruff, and as a skin cleanser maybe formulated as follows.

[0341] Glycolide powder 1.0 g is dissolved in ethanol 89 ml andpropylene glycol 10 ml. The composition thus formulated has pH 4.0, andcontains 1% active ingredient.

EXAMPLE 53

[0342] A typical composition containing a dimeric form of alphahdyroxyacid in ointment for dry skin, psoriasis, eczema, pruritus,wrinkles and other skin changes associated with aging may be formulatedas follows.

[0343] Glycolide powder 2.0 g is mixed uniformly with petrolatum 66 gand mineral oil 32 g. The composition thus formulated contains 2% activeingredient.

EXAMPLE 54

[0344] A typical composition containing a full strength or a highconcentration of an alpha hydroxyacid, alpha ketoacid or closely relatedcompound for topical treatments of warts, keratoses, acne, age spots,nail infections, wrinkles and aging related skin changes may be preparedas follows.

[0345] If the alpha hydroxyacid, alpha ketoacid or closely relatedcompound at full strength is a liquid form at room temperature such as2-hydroxypropanoic acid, 2-ketopropanoic acid, methyl 2-ketopropanoateand ethyl 2-ketopropanoate, the compound is directly dispensed as 0.5 to1 ml aliquots in small vials. If the compound is a solid form at roomtemperature such as 2-hydroxyethanoic acid and 2-methyl2-hydroxypropanoic acid, it is first dissolved in minimal amount of anappropriate solvent or solvent system such as water or ethanol andpropylene glycol with or without a gelling agent. For example,2-hydroxyethanoic acid 70 g is dissolved in water 30 ml, and the 70%strength 2-hydroxyethanoic acid thus obtained is dispensed as 0.5 to 1ml aliquots in small vials. If a gelling agent is used, methyl celluloseor hydroxyethyl cellulose 1 g may be added to the above solution.

EXAMPLE 55

[0346] A typical composition containing an intermediate strength of analpha hydroxyacid, alpha ketoacid or closely related compound fortopical treatment of warts, keratoses, acne, nail infections, age spots,wrinkles and aging related skin changes may be prepared as follows.

[0347] 2-Hydroxyethanoic acid or 2-ketopropanoic acid 40 g is dissovledin ethanol 54 g and propylene glycol 6 g, and the 40% strength solutionthus obtained is dispensed as 5 to 10 ml aliquots in dropper bottles.

Test Results

[0348] In order to determine whether amphoteric and pseudoamphotericcompositions of the instant invention were therapeutically effective forvarious cosmetic conditions and dermatologic disorders, a total of morethan 90 volunteers and patients participated in these studies. Someparticipating subjects were given two preparations; an amphoteric orpseudoamphoteric composition containing an alpha hydroxyacid or therelated compound, and a vehicle placebo. Others were given multiplepreparations containing a known pharmaceutical agent such as acorticosteroid with or without incorporation of an amphoteric orpseudoamphoteric composition consisting of an alpha hydroxyacid or therelated compound of the instant invention. The amphoteric andpseudoamphoteric compositions were formulated according to the Examplesdescribed in the previous section.

[0349] 1. Common dry skin.

[0350] Human subjects having ordinary dry skin or with moderate degreesof dry skin as evidenced by dryness, flaking and cracking of the skinwere instructed to apply topically the lotion, cream or ointmentcontaining an alpha hydroxyacid or the related compound in amphoteric orpseudoamphoteric composition, on the affected area of the skin. Topicalapplication, two to three times daily, was continued for two to fourweeks.

[0351] In all the 28 subjects tested, the feeling of the skin drynessdisappeared within a week of topical application. The rough and crackedskin became less pronounced and the skin appeared normal and felt smoothafter several days of topical treatment. The alpha hydroxyacids and therelated compounds which have been found to be therapeutically effectivewhen incorporated into the amphoteric or pseudoamphoteric compositionsfor dry skin are as follows:

[0352] 2-hydroxyethanoic acid (glycolic acid), 2-hydroxypropanoic acid(lactic acid), 2-methyl-2-hydroxypropanoic acid (methyllactic acid),phenyl 2-hydroxyethanoic acid (mandelic acid), phenyl2-methyl-2-hydroxyethanoic acid (atrolactic acid),3-phenyl-2-hydroxypropanoic acid (phenyllactic acid), diphenyl2-hydroxyethanoic acid (benzilic acid), gluconolactone, tartaric acid,citric acid, saccharic acid, malic acid, tropic acid, glucuronic acid,galacturonic acid, gluconic acid, 3-hydroxybutanoic acid, quinic acid,ribonolactone, glucuronolactone, galactonolactone, pyruvic acid, methylpyruvate, ethyl pyruvate, phenylpyruvic acid, benzoylformic acid andmethyl benzoylformate.

[0353] The ordinary dry skin conditions, once restored to normalappearing skin, remained improved for some time until causes of dryskin, such as low humidity, cold weather, excessive contact pressure,detergents, soaps, solvents, chemicals, etc., again caused recurrence ofthe dry skin condition. On continued use it was also found that twicedaily topical application of an amphoteric or pseudoamphotericcomposition containing an alpha hydroxyacid or the related compound ofthe instant invention prevented the development of new dry skin lesions.

[0354] 2. Severe dry skin.

[0355] In severe dry skin, the skin lesions are different from theordinary dry skin. A main cause of severe dry skin is inherited geneticdefects of the skin. The involved skin is hyperplastic, fissured and hasthick adherent scales. The degree of thickening is such that lesions arepalpably and visually elevated. The thickened adherent scales cause thesurface of involved skin to be markedly rough and uneven. These twoattributes of thickness and texture can be quantified to allow objectivemeasurement of degree of improvement from topically applied testmaterials as follows: DEGREE OF IMPROVEMENT Sub- None Mild Moderatestantial Complete (0) (1+) (2+) (3+) (4+) Thickness Highly DetectableReadily Barely Normal elevated reduction apparent elevated thicknessreduction Texture Visibly Palpably Uneven but Slightly Visibly and roughrough not rough uneven palpably smoc

[0356] By means of such parameters, degrees of change in lesions can benumerically recorded and comparisons made of one treated site toanother.

[0357] In order to evaluate the amphoteric and pseudoamphotericcompositions of the instant invention, a total of 6 patients havingsevere dry skin conditions were treated with the compositions containingan alpha hydroxyacid or the related compound.

[0358] Tested areas were of a size convenient for topical applications,i.e., circles 5 cm in diameter demarcated with a plastic ring of thatsize inked on a stamp pad. The medicinal lotions or creams weretopically applied by the patient in an amount sufficient to cover thetreatment sites. Applications were made three times daily and withoutocclusive dressings. Applications were discontinued at any time whenresolutions of the lesion on the treatment area was clinically judged tobe complete.

[0359] The test results of amphoteric and pseudoamphoteric compositionscontaining the following alpha hydroxyacids or the related compounds onpatients with severe dry skin are summarized as follows:

[0360] 4+ Effectiveness; glycolic acid, lactic acid, methyllactic acid,mandelic acid, tropic acid, atrolactic acid and pyruvic acid.

[0361] 3+ Effectiveness; benzilic acid, gluconolactone, malic acid,tartaric acid, citric acid, saccharic acid, methyl pyruvate, ethylpyruvate, phenyllactic acid, phenylpyruvic acid, glucuronic acid and3-hydroxybutanoic acid.

[0362] 2+ Effectiveness; mucic acid, ribonolactone, 2-hydroxydodecanoicacid, quinic acid, benzoylformic acid and methyl benzoylformate.

[0363] 3. Psoriasis.

[0364] The involved skin in psoriasis is hyperplastic (thickened),erythematous (red or inflamed), and has thick adherent scales. Thedegree of thickening is such that lesions are elevated up to 1 mm abovethe surface of adjacent normal skin; erythema is usually an intense red;the thickened adherent scales cause the surface of involved skin to bemarkedly rough and uneven. These three attributes of thickness, colorand texture can be quantified to allow objective measurement of degreeof improvement from topically applied test materials as follows. DEGREEOF IMPROVEMENT Sub- None Mild Moderate stantial Complete (0) (1+) (2+)(3+) (4+) THICKNESS Highly Detectable Readily Barely Normal elevatedreduction apparent elevated thickness reduction TEXTURE Visibly PalpablyUneven Slightly Visibly rough rough but not uneven and rough palpablysmooth COLOR Intense Red Dark Pink Light Pink Normal Red Skin Color.

[0365] By means of such parameters, degree of improvement in psoriaticlesions can be numerically recorded and comparisons made of one treatedsite to another.

[0366] Patients having psoriasis participated in this study. Amphotericand pseudoamphoteric compositions containing both an alpha hdyroxyacidor the related compound and a corticosteroid were prepared according tothe Examples. Compositions containing only a corticosteroid were alsoprepared and included in the comparison test. Test areas were kept tominimal size convenient for topical application, i.e., circlesapproximately 4 cm in diameter. The medicinal compositions weretopically applied by the patient in an amount (usually about 0.1milliliter) sufficient to cover the test site. Applications were madetwo to three times daily and without occlusive dressings. Test periodsusually lasted for two to four weeks. The test results on patientshaving psoriasis are summarized on the following table. Topical Effectson Psoriasis of Antipsoriatic Compositions Therapeutic Compositions*Effectiveness Hydrocortisone 2.5% alone 1+ With lactic acid 2+ Withglycolic acid 2+ With ethyl pyruvate 2+ With methyl pyruvate 2+ Withbenzilic acid 2+ With pyruvic acid 2+ With methyllactic acid 2+Hydrocortisone 17-valerate 0.2% alone 2+ With lactic acid 3+ Withglycolic acid 3+ With benzilic acid 3+ With ethyl pyruvate 3+ Withmethyl pyruvate 3+ With gluconolactone 3+ With pyruvic acid 3+Betamethasone dipropionate 0.05% alone 3+ With lactic acid 4+ Withglycolic acid 4+ With ethyl pyruvate 4+ With methyl pyruvate 4+ Withmandelic acid 4+ With benzilic acid 4+ Clobetasol propionate 0.05% alone3+ With lactic acid 4+ With glycolic acid 4+ With ethyl pyruvate 4+ Withmethyl pyruvate 4+ With methyllactic acid 4+ With mandelic acid 4+ Withtropic acid 4+ With benzilic acid 4+

[0367] We have also found that an amphoteric or pseudoamphotericcomposition containing an alpha hydroxyacid or the related compound incombination with an antimetabolite agent such as 5-fluorouracil with orwithout additional incorporation of a corticosteroid is therapeuticallyeffective for topical treatment of psoriasis.

[0368] 4. Eczema.

[0369] In a topical treatment of eczema patients, hydrocortisone aloneat 2.5% or hydrocortisone 17-valerate alone at 0.2% would achieve only2+ improvement, and betamethasone dipropionate or clobetasol propionatealone at 0.05% would achieve only a 3+ improvement on all the eczemapatients tested. Test results of amphoteric and pseudoamphotericcompositions containing both a corticosteroid and one of the followingalpha hydroxyacids or the related compounds are shown as follows:

[0370] 3+ Effectiveness; hydrocortisone 2.5% or hydrocortisone17-valerate 0.2% plus lactic acid, glycolic acid, mandelic acid, ethylpyruvate, gluconolactone, benzilic acid or ribonolactone.

[0371] 4+ Effectiveness; betamethasone dipropionate or clobetasolpropionate 0.05% plus lactic acid, glycolic acid, mandelic acid, ethylpyruvate, methyl pyruvate, benzilic acid, gluconolactone, citric acid,tartaric acid or methyllactic acid.

[0372] 5. Oily Skin and Skin Cleanse.

[0373] Human subjects having oily skin or blemished skin as well as acnepatients having extremely oily skin participated in this study.Amphoteric and pseudoamphoteric compositions containing alphahydroxyacids or the related compounds were formulated in solution or gelform.

[0374] Each participating subject received a solution or a gelpreparation containing an alpha hydroxyacid or a related compound in anamphoteric or pseudoamphoteric composition. The participating subjectswere instructed to apply topically the solution or gel medication on theaffected areas of forehead or other part of the face. Three times dailyapplications were continued for 2 to 6 weeks.

[0375] The degree of improvement of oily skin as well as the rate ofimprovement of acne lesions were clinically evaluated. Most participantsreported that oiliness of skin disappeared within one to two weeks oftopical administration, and the skin so treated became smooth and soft.Many participating subjects preferred gel preparations than solutioncompositions. It was found that all the participants showed substantialimprovements on oily skin and acne lesions by six weeks of topicaladministration of amphoteric or pseudoamphoteric compositions containingalpha hydroxyacids or the related compounds of the instant invention.

[0376] Those alpha hydroxyacids and the related compounds which havebeen found to be therapeutically effective for oily skin and as skincleansers include: benzilic acid, glycolic acid, lactic acid,methyllactic acid, mandelic acid, pyruvic acid, ethyl pyruvate, methylpyruvate, tropic acid, malic acid, gluconolactone, 3-hydroxybutanoicacid, glycolide and polyglycolic acid. As a skin cleanser for oily skinor acne-prone skin, the amphoteric or pseudoamphoteric compositioncontaining an alpha hydroxyacid or the related compound may also beincorporated with other dermatologic agents. For example, an amphotericgel composition may consist of both an alpha hydroxyacid anderythromycin or tetracycline.

[0377] 6. Acne

[0378] Amphoteric and pseudoamphoteric compositions containing alphahydroxyacids or the related compounds of the instant invention in asolution or gel form were provided to patients having comedongenicand/or papulopustular lesions of acne. Each participating patient wasinstructed to apply topically the composition on the involved areas ofthe skin such as forehead, face and chest. Three times dailyadministration was continued for 6 to 12 weeks.

[0379] The degree and rate of improvement on acne lesions wereclinically evaluated. It was found that acne lesions consisting mainlyof comedones improved substantially after 6 to 8 weeks of topicaladministration with the amphoteric or the pseudoamphoteric compositioncontaining an alpha hydroxyacid or the related compound. The time forcomplete clearing of comedongenic acne treated with the amphoteric orpseudoamphoteric composition of the instant invention varied from 6 to12 weeks.

[0380] As a topical treatment for papulopustular and/or pustular acnethe amphoteric or pseudoamphoteric composition containing an alphahydroxyacid or the related compound may incorporate in addition anantiacne agent. The antiacne agents include antibiotics such aserythromycin, tetracycline, clindamycin, meclocycline and minocycline,and retinoids such as retinoic acid. Such combination compositions havebeen found to be therapeutically more effective for topical treatment ofsevere acne.

[0381] 7. Age Spots

[0382] Many small and large discolored lesions, commonly called agespots on the face and the back of the hands are benign keratoses, ifthey are not variants of actinic keratoses. Very few of such age spotsare true lentigines, therefore alpha hydroxyacids and the relatedcompounds may be effective in eradicating most age spots withoutconcurrent use of skin bleaching agents such as hydroquinone andmonobenzone. However, additional beneficial effects have been found whena skin bleaching agent such as hydroquinone or monobenzone is alsoincorporated into the compositions of the instant invention for agespots involving pigmented lesions.

[0383] Amphoteric and pseudoamphoteric compositions containing alphahydroxyacids or the related compounds, with or without incorporation ofhydroquinone were provided to volunteer subjects and patients having agespot keratoses, melasma, lentigines and/or other pigmented lesions. Eachparticipating subject received two products, i.e., with or without theaddition of 2% hydroquinone to the amphoteric or pseudoamphotericcomposition containing an alpha hydroxyacid or the related compound.

[0384] The volunteer subjects and patients were instructed to applytopically one medication on one side of the body such as left side ofthe face or on the back of the left hand, and the other medication onthe other side of the body such as on right side of the face or on theback of the right hand. Specific instructions were given to theparticipating subjects that the medications were applied three timesdaily to the lesions of age spot keratoses, melasmas, lentigines and/orother pigmented lesions. Clinical photos were taken of participatingsubjects before the initiation of the topical treatment and every 4weeks during the course of treatment.

[0385] At the end of 4 to 8 weeks, improvement of age spot keratoses wasclinically discernible. After 4 to 6 months of topical treatment,substantial improvement of age spot keratoses occurred in the majorityof subjects tested. Complete eradication of age spot keratoses occurredafter 6 to 9 months of topical administration with the amphoteric orpseudoamphoteric compositions of the instant inventions.

[0386] Amphoteric or pseudoamphoteric compositions containing both analpha hydroxyacid or the related compound and hydroquinone were judgedto be more effective in eradicating pigmented age spots, melasma,lentigines and other pigmented lesions.

[0387] The alpha hydroxyacids and the related compounds which have beenfound to be therapeutically effective for age spots with or withoutcombination with hydroquinone include glycolic acid, lactic acid,methyllactic acid, mandelic acid, pyruvic acid, methyl pyruvate, ethylpyruvate, benzilic acid, gluconolactone, malic acid, tartaric acid,citric acid and tropic acid. For flat or slightly elevated seborrheickeratoses on the face and/or the back of the body, amphoteric orpseudoamphoteric compositions containing higher concentrations of alphahydroxyacids or the related compounds have been found to be effective ineradicating such lesions.

[0388] Actinic keratoses may be successfully treated with amphoteric orpseudoamphoteric compositions containing alpha hydroxyacids or therelated compounds in combination with an antimetabolite agent such as5-fluorouracil.

[0389] 8. Warts.

[0390] Eradications of common warts by topical application of amphotericor pseudoamphoteric compositions require higher than usualconcentrations of alpha hydroxyacids or the related compounds in theformulations. The amphoteric or pseudoamphoteric compositions wereformulated as a liquid or light gel form, and dispensed usually as 0.5-1ml aliquots in small vials.

[0391] Topical applications were made discreetly to wart lesions byadult patients or by responsible adult family members. For ordinaryusual warts of hands, fingers, palms and soles topical applications weremade 2 to 4 times daily, and were continued for 2 to 6 weeks. Generally,the overlying stratum corneum of the wart lesion change in appearanceafter several weeks topical application of the composition. In mostcases, the wart lesion simply fell off. The skin then healed normallywithout forming any scars.

[0392] We have also found that when a dermatologic agent such as5-fluorouracil is incorporated into the amphoteric or pseudoamphotericcompositions containing alpha hydroxyacids or the related compounds, themedications have been very effective for topical treatment of wartswithout using higher concentrations of alpha hydroxyacids or the relatedcompounds.

[0393] The alpha hydroxyacids and the related compounds which have beenfound to be therapeutically effective for topical treatment of wartswith or without incorporation of 5-fluorouracil include glycolic acid,lactic acid, pyruvic acid, ethyl pyruvate, methyl pyruvate and mandelicacid.

[0394] Topical formulations and compositions containing specific alphahydroxyacids, alpha ketoacids or the related compounds at full strengthsor high to intermediate concentrations prepared according to Examples 54and 55, without utilizing amphoteric or pseudoamphoteric systems, havealso been tested for ordinary warts of the hands, fingers, palms andsoles. Participating patients have been advised to apply a small drop ofthe medication with a toothpick or a fine caliber brush to the center ofa wart lesion only. Prescirbed applications have been 3 to 6 timesdaily, and are continued until the patient feels pain.

[0395] For the more rough-surfaced wart, the duration of application hasbeen as short as one or a few days. For lesions with more compact, lesspermeable stratum corneum, the time to experience gpain has been longer.Frequency and duration of applications have been modified according toother clinical responses and reactions of lesions, and the patient orresponsible family member is instructed accordingly.

[0396] For example, some clinical manifestations other than pain havealso been used as a signal to interrupt application. Thesemanifestations have included distinct blanching of the lesions ordistinct peripheral erythema. Very often, discomfort is the usual signalof clinical reactions.

[0397] Generally, the overlying stratum corneum of the wart lesionsbecame loose, and the whole wart lesion simply fell off. The skin thenhealed normally without forming any scars.

[0398] 9. Athlete's Foot and Nail Infections

[0399] Amphoteric and pseudoamphoteric compositions containing both anantifungal agent and one of the alpha hydroxyacids or the relatedcompounds were provided to patients having frequent recurrence of fungalinfections involving the foot. The antifungal agents includeclotrimazole, miconazole, ketoconazole and griseofulvin. When both feetbut not toe nails were involved in the infection, the patients wereinstructed to apply topically the compositions of the instant inventionon the left foot, and a brand-name antifungal product on the right foot.Three times daily applications were continued for one to four weeks. Thedegree and rate of improvement on skin lesions were clinicallyevaluated, and comparison was made one side of the body against theother. It was found that the skin lesions improved much faster with theamphoteric or pseudoamphoteric compositions containing both theantifungal agent and the alpha hydroxyacid or the related compound. Thealpha hydroxyacids or the related compounds seemed to enhance theefficacies of the antifungal agents, and also to eliminate thediscomforts such as itching, tingling, burning and irritation due tofungal infections. When toe nails were not involved the infected skingenerally healed within one to two weeks from topical application of theamphoteric or pseudoamphoteric composition containing both an antifungalagent and an alpha hydroxyacid or the related compound.

[0400] Fungal infections of the nails are very difficult to treat,because antifungal products to date are not therapeutically effectivefor topical treatment of nails. One of the reasons is that mostantifungal drugs have not been formulated as bioavailable forms in thecommercial products. When tow nails were involved in the infections,patients were provided with amphoteric or pseudoamphoteric compositionscontaining in combination an antifungal agent and an alpha hydroxyacidranging from 20 to 99%, dispensed as 1-2 ml aliquots in small vials. Thepatients were instructed to apply topically the compositions discreetlyto the infected nail surface by means of a fine calibre paint brush. thetechnique was the same as for application of nail polish, that iscareful avoidance of contact with lateral nail folds or any peri-ungualskin. once or twice daily applications were continued for 2 to 8 weeks.

[0401] As mentioned above, while brand-name antifungal products areusually not effective against fungus infections within or underneath thenail, it was found that the amphoteric or pseudoamphoteric compositionscontaining an antifungal agent and an alpha hydroxyacid or alphaketoacid were therapeutically effective in eradicating fungal infectionsof the nails. Such treatment may cause in some instances the treatednail plate to become loose and eventually fell off from the nail bed.This happened quite naturally without any feeling of pain nor bleeding,and the skin lesion healed quickly with normal growth of a new nail.

[0402] 10. Wrinkles

[0403] Wrinkles of skin may be due to natural aging and/or sun damage.Most fine wrinkles on the face are due to natural or innate aging, whilecoarse wrinkles on the face are the consequence of actinic or sundamage. Although the real mechanism of wrinkles formation in the skin isstill unknown, it has been shown that visible fine wrinkles are due todiminution in the number and diameter of elastic fibers in the papillarydermis, and also due to atrophy of dermis as well as reduction insubcutaneous adipose tissue. Histopathology and electron microscopystudies indicate that coarse wrinkles are due to excessive deposition ofabnormal elastic materials in the upper dermis and thickening of theskin. At present there are no commercial products which have been foundto be therapeutically effective for topical eradication of wrinkles,although retinoic acid (tretinoin) has been shown to be beneficial forsun damaged skin.

[0404] In order to determine whether the amphoteric or pseudoamphotericcomposition containing the alpha hydroxyacids, alpha ketoacids or therelated compounds are therapeutically effective for wrinkles, patientsand volunteer subjects participated in this study. The participants wereinstructed to apply the formulations of the instant invention twicedaily on areas of facial wrinkles for 4 to 12 months. All participantswere told to avoid sun exposure, and to use sunscreen products ifexposure to sunlight was unavoidable. Photographs of each side of theface for each participant were taken at the beginning of the study andrepeated at one to three-month intervals. The participants were askednot to wear any facial make-up at the time of each office visit.Standardized photographic conditions were used including the use of samelot of photographic film, the same light source at two feet from theface, aimed at a locus on the frontal aspect of each cheek. Each timephotographs were taken with camera aimed perpendicular to the cheek. Atthe end of study twenty two participants had been entered into the studyfor at least four months. Clinical evaluations and review of photographshave revealed substantial reductions in facial wrinkles of the temporalregion and cheek area on at least one side of the face in eighteencases. Degree of improvement and reduction in wrinkles has beenevaluated and determined to be mild to moderate in six participants butvery substantial in twelve participants.

[0405] The alpha hydroxyacids, alpha ketoacids and other relatedcompounds including their lactone forms which may be incorporated intothe amphoteric and pseudoamphoteric compositions for cosmetic conditionsand dermatologic disorders such as dry skin, acne, age spots, keratoses,warts and skin wrinkles or in combination with other dermatologic agentsto enhance therapeutic effects include the following:

[0406] (1) Alkyl Alpha Hydroxyacids

[0407] 2-Hydroxyethanoic acid (Glycolic acid), 2-Hydroxypropanoic acid(Lactic acid), 2-Methyl 2-hydroxypropanoic acid (Methyllactic acid),2-Hydroxybutanoic acid, 2-Hydroxypentanoic acid, 2-Hydroxyhexanoic acid,2-Hydroxyheptanoic acid, 2-Hydroxyoctanoic acid, 2-Hydroxynonanoic acid,2-Hydroxydecanoic acid, 2-Hydroxyundecanoic acid, 2-Hydroxydodecanoicacid (Alpha hydroxylauric acid), 2-Hydroxytetradecanoic acid (Alphahydroxymyristic acid), 2-Hydroxyhexadecanoic acid (Alpha hydroxypalmiticacid), 2-Hydroxyoctadecanoic acid (Alpha hydroxystearic acid),2-Hydroxyeicosanoic acid (Alpha hydroxyarachidonic acid).

[0408] (2) Aralkyl And Aryl Alpha Hydroxyacids

[0409] 2-Phenyl 2-hydroxyethanoic acid (Mandelic acid), 2,2-Diphenyl2-hydroxyethanoic acid (Benzilic acid), 3-Phenyl 2-hydroxypropanoicacid. (Phenyllactic acid), 2-Phenyl 2-methyl 2-hydroxyethanoic acid(Atrolactic acid), 2-(4′-Hydroxyphenyl) 2-hydroxyethanoic acid,2-(4′-Clorophenyl) 2-hydroxyethanoic acid,2-(3′-Hydroxy-4′-methoxyphenyl) 2-hydroxyethanoic acid,2-(4′-Hydroxy-3′-methoxyphenyl) 2-hydroxyethanoic acid,3-(2′-Hydroxyphenyl) 2-hydroxypropanoic acid, 3-(4′-Hydroxyphenyl)2-hydroxypropanoic acid, 2-(3′,4′-Dihydroxyphenyl) 2-hydroxyethanoicacid.

[0410] (3) Polyhydroxy Alpha Hydroxyacids

[0411] 2,3-Dihydroxypropanoic acid (Glyceric acid),2,3,4-Trihydroxybutanoic acid (Isomers; erythronic acid, threonic acid),2,3,4,5-Tetrahydroxypentanoic acid (Isomers; ribonic acid, arabinoicacid, xylonic acid, lyxonic acid), 2,3,4,5,6-Pentahydroxyhexanoic acid(Isomers; aldonic acid, altronic acid, gluconic acid, mannoic acid,gulonic acid, idonic acid, galactonic acid, talonic acid),2,3,4,5,6,7-Hexahydroxyheptanoic acid (Isomers; glucoheptonic acid,galactoheptonic acid, etc.)

[0412] (4) Polycarboxylic Alpha Hydroxyacids

[0413] 2-Hydroxypropane-1,3-dioic acid (Tartronic acid),2-Hydroxybutane-1,4-dioic acid (Malic acid),2,3-Dihydroxybutane-1,4-dioic acid (Tartaric acid),2-Hydroxy-2-carboxypentane-1,5-dioic acid (Citric acid),2,3,4,5-Tetrahydroxyhexane-1,6-dioic acid (Isomers; saccharic acid,mucic acid, etc.)

[0414] (5) Alpha Hydroxyacid Related Compounds

[0415] Ascorbic acid, quinic acid, isocitric acid, tropic acid,3-chlorolactic acid, trethocanic acid, cerebronic acid, citramalic acid,agaricic acid, 2-hydroxynervonic acid and aleuritic acid.

[0416] (6) Alpha Ketoacids And Related Compounds

[0417] 2-Ketoethanoic acid (Glyoxylic acid), Methyl 2-ketoethanoate,2-Ketopropanoic acid (Pyruvic acid), Methyl 2-ketopropanoate (Methylpyruvate), Ethyl, 2-ketopropanoate (Ethyl pyruvate), Propyl2-ketopropanoate (Propyl pyruvate), 2-Phenyl-2-ketoethanoic acid(Benzoylformic acid), Methyl 2-phenyl-2-ketoethanoate (MEthylbenzoylformate), Ethyl 2-phenyl-2-ketoethanoate (Ethyl benzoylformate),3-Phenyl-2-ketopropanoic acid (Phenylpyruvic acid), Methyl3-phenyl-2-ketopropanoate (Ethyl phenylpyruvate), 2-Ketobutanoic acid,2-Ketopentanoic acid, 2-Ketohexanoic acid, 2-Ketoheptanoic acid,2-Ketooctanoic acid, 2-Ketododecanoic acid, Methyl 2-ketooctanoate

[0418] The amphoteric and pseudoamphoteric compounds which may beincorporated into the compositions of the instant invention for cosmeticand dermatologic conditions include amino acids, peptides, polypeptides,proteins and the like compounds such as creatinine and creatine.

[0419] The dimeric and polymeric forms of alpha hydroxyacids and therelated comopounds which may be incorporated into the compositions ofthe instant invention include acyclic esters and cyclic ester; forexample, glycolyl glycollate, lactyl lactate, glycolide, lactide,polyglycolic acid and polylactic acid.

[0420] The invention may be embodied in other specific forms withoutdeparting from the spirit or essential characteristics thereof. Thepresent embodiments are therefore to be considered in all respects asillustrative and not restrictive, the scope of the invention beingindicated by the appended claims and all changes which come within themeaning and equivalency of the claims are therefore intended to beembraced therein.

1. A composition comprising in combination an amphoteric orpseudoamphoteric agent and an alpha hydroxyacid, an alpha ketoacid orthe related cmpound in a pharmaceutically acceptable vehicle for topicaltreatment of cosmetic conditions or dermatologic disorders.
 2. Thecomposition of claim 1 wherein said amphoteric or pseudoamphotwericagent is at least one member selected from the group consisting of aminoacids, dipeptides, polypeptides, proteins, imidazoline derivatives,lecithin derivatives, or metallic oxides.
 3. The composition of claim 1wherein said amphoteric or pseudoamphoteric agent is at lesat one memberselected from the group consisting of glycine, alanine, valine, leucine,isoleucine, serine, threonine, cysteine, cystine, methionine, asparticacid, asparagine, glutamic acid, glutamine, arginine, lysine,5-hydroxylysine, histidine, phenylalanine, tyrosine, tryptophan,3-hydroxyproline, 4-hydroxyproline, proline, homocysteine, homocystine,homoserine, ornithine, citrulline, creatine, creatinine,3-aminopropanoic acid, 2-aminobutanoic acid, 4-aminobutanoic acid,2-amino-2-methylpropanoic acid, 2-methyl-3-aminopropanoic acid,theanine, phenylglycine, canavanine, canaline, 4-hydroxyarginine,4-hydroxyornithine, homoarginine, 4-hydroxyhomoarginine, β-lysine,2,4-diaminobutanoic cid, 2,3-diaminopropanoic acid, 2,6-diaminopimelicacid, 2-amino-3-phenylbutanoic acid, 2-methylserine, 3-phenylserine,betaine, taurine, cysteinesulfinic acid, methionine sulfoxide,methionine sulfone, 3,5-diiodotyrosine, thyroxine, monoiodotyrosine,pipecolic acid, 4-aminopipecolic acid, 4-methylproline, glycylglycine,carnosine, anserine, ophidine, homocarnosine, β-alanyllysine,β-alanylarginine, glutathione, ophthalmic acid, norophthalmic acid,bradykinin, glucagon, protamines, histones, cocoamphoglycine,cocoamphopropionate, cocoamphopropylsulfonate, phosphatidylethanolamine, phosphatidyl serine, sphingomyelin, stearamidoethyldiethylamine, stearamidoethyl diethanolamine, stearamidopropyldimethylamine, quaternary ammonium hydroxide, quaternium hydorxide,aluminum oxide or zinc oxide.
 4. The composition of claim 1 wherein saidalpha hydroxyacid is at least one member selected from the gruopconsisting of alkyl alpha hdyroxyacid, aralkyl and aryl alphahydroxyacid, polyhydroxy alpha hydroxyacid and polycarboxylic alphahydroxyacid having the following chemical formula: (Ra) (Rb) C (OH) COOHwherein Ra and Rb are H, F, Cl, Br, alkyl, aralkyl or aryl group ofsaturated or unsaturated, isomeric or non-isomeric, straight or branchedchain or cyclic form, having 1 to 25 carbon atoms, and in addition Raand Rb may carry OH, CHO, COOH and alkoxy group having 1 to 9 carbonatoms, said alpha hydroxyacid existing as a free acid or lactone form,or in salt form with an organic base or an inorganic alkali, and asstereoisomers as D, L, and DL forms when Ra and Rb are not identical. 5.The composition of claim 4 wherein said alkyl alpha hydroxyacid is atleast one member selected from the group consisting of 2-Hydroxyethanoicacid (Glycolic acid), 2-Hydroxypropanoic acid (Lactic acid), 2-Methyl2-hydroxypropanoic acid (Methyllactic acid), 2-Hydroxybutanoic acid,2-Hydroxypentanoic acid, 2-Hydroxyhexanoic acid, 2-Hydroxyheptanoicacid, 2-Hydroxyoctanoic acid, 2-Hydroxynonanoic acid, 2-Hydroxydecanoicacid, 2-Hydroxyundecanoic acid, 2-Hydroxydodecanoic acid, (Alphahydroxylauric acid), 2-Hydroxytetradecanoic acid (Alpha hydroxymyristicacid), 2-Hydroxyhexadecanoic acid (Alpha hydroxypalmitic acid),2-Hydroxyoctadecanoic acid (Alpha hydroxystearic acid),2-Hydroxyeicosanoic acid (Alpha hydroxyarachidonic acid).
 6. Thecomposition of claim 4 wherein said aralkyl and aryl alpha hydroxyacidis selected from the group consisting of 2-Phenyl 2-hydroxyethanoic acid(Mandelic acid), 2,2-Diphenyl 2-hydroxyethanoic acid (Benzilic acid),3-Phenyl 2-hydroxypropanoic acid (Phenyllactic acid), 2-Phenyl 2-methyl2-hydroxyethanoic acid (Atrolactic acid), 2-(4′-Hydroxyphenyl)2-hydroxyethanoic acid, 2-(4′-Chlorophenyl) 2-hydroxyethanoic acid,2-(3′-Hyroxy-4′-methoxyphenyl) 2-hydroxyethanoic acid,2-(4′-Hydroxy-3′-methoxypehenyl) 2-hydroxyethanoic acid,3-(2′-Hydroxyphenyl) 2-hydroxypropanoic acid, 3-(4′-Hydroxyphenyl)2-hyroxypropanoic acid, or 2-(3′,4′-Dihydroxyphenyl) 2-hydroxyethanoicacid.
 7. The composition of claim 4 wherein said polyhydroxy alphahydroxyacid and polycarboxylic alpha hydroxyacid is at least one memberselected from the group consisting of 2,3-Dihydroxypropanoic acid(Glyceric acid), 2,3,4-Trihydroxybutanoic acid (Isomers; erythronicacid, threonic acid), 2,3,4,5-Tetrahydroxypentanoic acid (Isomers;ribonic acid, arabinoic acid, xylonic acid, lyxonic acid),2,3,4,5,6-Pentahydroxyhexanoic acid (Isomers; allonic acid, altronicacid, gluconic acid, mannoic acid, gulonic acid, idonic acid galactonicacid, talonic acid), 2,3,4,5,6,7-Hexahydroxyheptanoic acid (Isomers;glucoheptonic acid, galactoheptonic acid etc.),2-Hydroxypropane-1,3-dioic acid (Targtronic acid),2-Hydroxybutane-1,4-dioic acid (Malic acid),2,3-Dihydroxybutane-1,4-dioic acid (Tartaric avcid),2-Hydroxy-2-carboxypentane-1,5-dioic acid (Citric acid),2,3,4,5-Tetrahydroxyhexane-1,6-dioic acid (Isomers; saccharic acid,mucic acid, etc.), or lactone forms (gluconolactone, galactonolactone,glucuronolactone, galacturonolactone, gulonolactone, ribonolactone,saccharic acid lactone, pantoyllactone, glucoheptonolactone,mannonolactone, galactoheptonolactone, etc.).
 8. The composition ofclaim 1 wherein said alpha ketoacid is at least one member selected froma group of compounds having the following chemical formula: (Ra) COCOO(Rb) wherein Ra and Rb are H, alkyl, aralkyl or aryl group ofsaturated or unsaturated, isomeric or non-isomeric, straight or branchedchain or cyclic form, having 1 to 25 carbon atoms, and in addition Ramay carry F, Cl, Br, I, OH, CHO, COOH and alkoxy group having 1 to 9carbon atoms, said alpha ketoacid existing as a free acid or an esterform, or in a salt form with an organic base or an inorganic alkali. 9.The composition of claim 8 wherein said alpha ketoacid and its ester isat least one member selected from the group consisting of 2-Ketoethanoicacid (Glyoxylic acid), Methyl 2-ketoethanoate, 2-Ketopropanoic acid(Pyruvic acid), Methyl 2-ketopropanoate (Methyl pyruvate), Ethyl2-ketopropanoate (Ethyl pyruvate), Propyl 2-ketopropanoate (Propylpyruvate), 2-Phenyl-2-ketoethanoic acid (Benzoylformic acid), Methyl2-phenyl-2-ketoethanoate (Methyl benzoylformate), Ethyl2-phenyl-2-ketoethanoate (Ethyl benzoylformate),3-Phenyl-2-ketopropanoic acid (Phenylpyruvic acid), Methyl3-phenyl-2-ketopropanoate (Methyl phenylpyruvate), Ethyl3-phenyl-2-ketopropanoate (Ethyl phenylpyruvate), 2-Ketobutanoic acid,2-Ketopentanoic acid, 2-Ketohexanoic acid, 2-Ketopheptanoic acid,2-Ketooctanoic acid, 2-Ketododecanoic acid, or Methyl 2-ketooctanoate.10. The composition of claim 1 wherein said the related compound is atleat one member selected from the group consisting of ascorbic acid,quinic acid, isocitric acid, tropic acid, trethocanic acid,3-chlorolactic acid, cerebronic acid, citramalic acid, agaricic acid,2-hydroxynervonic acid, aleuritic acid and pantoic acid.
 11. Theposition of claim 1 wherein said cosmetic conditions and dermatologicdisorders include dry skin, zerosis, ichthyosis, dandruff, brownishspots, keratoses, melasma, lentigines, age spots, liver spots, pigmentedspots, wrinkles, blemishes, skin lines, oily skin, acne, warts, eczema,pruritic skin, psoriasis, inflammatory dermatoses, disturbedkeratinization, skin changes associated with aging, nail or skinrequiring cleansers, conditioning or treatment, and hair or scalprequiring shampooing or conditioning.
 12. A composition comprising acosmetic or pharmaceutical agent in an amphoteric or pseudoamphotericsystem comprising an alpha hdyroxyacid, an alpha ketoacid or the relatedcompound in a pharmaceutically acceptable vehicle for topical treatmentof cosmetic conditions or medical disorders.
 13. The composition ofclaim 12 wherein said cosmetic or pharmaceutical agent is selected fromthe group consisting of agents that improve or eradicate age spots,keratoses and wrinkles; analgesics; anesthetics; antiacne agents;antibacterials; antiyeast agents; antifungal agents; antiviral agents;antidandruff agents; antidermatitis agents; antipruritic agents;antiemetics; antimotionsickness agents; antiinflammatory agents;antihyperkeratolytic agents; antidry skin agents; antiperspirants;antipsoriatic agents; antiseborrheic agents; hair conditioners and hairtreatment agents; antiaging and antiwrinkle agents; antiasthmatic agentsand bronchodilators; sunscreen agents; antihistamine agents; skinlightening agents; depigmenting agents; vitamines; corticosteroids;tanning agents; hormones; retinoids; topical cardiovascular agents ordermatologicals.
 14. The composition of claim 12 wherein said cosmeticor pharmaceutical agent is selected from the group consisting ofclotrimazole, ketoconazole, miconazole, griseofulvin, hydroxyzine,diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine,hydroquinone, monobenzone, erythromycin, tetracycline, clindamycin,meclocycline, minocycline, naproxen, ibuprofen, theophylline, cromolyn,albuterol, retinoic acid, 13-cis retinoic acid, hydrocortisone,hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone17-butyrate, betamethasone dipropionate, triamcinolone acetonide,fluocinonide, clobetasol propionate, benzoyl peroxide, crotamiton,propranolol, promethazine, vitamin A palmitate or vitamin E acetate. 15.The composition of claim 12 wherein said amphoteric or pseudoamphotericsystem is further comprising at least one amphoteric or pseudoamphotericagent selected from the group consisting of amino acids, dipeptides,polypeptides, proteins, imidazoline derivatives, lecithin derivatives,related agents or metallic oxides.
 16. The composition of claim 12further comprising at least one amphoteric or pseudoamphoteric agentselected from the group consisting of glycine, alanine, valine, leucine,isoleucine, serine, threonine, cysteine, cystine, methionine, asparticacid, asparagine, glutamic acid, glutamine, arginine, lysine,5-hydroxylysine, histidine, phenylalanine, tyrosine, tryptophan,3-hydroxyproline, 4-hydroxyproline, proline, homocysteine, homocystine,homoserine, ornithine, citruline, creatine, creatinine, 3-aminopropanoicacid, 2-aminobutanoic acid, 4-aminobutanoic acid,2-amino-2-methylpropanoic acid, 2-methyl-3-aminopropanoic acid,theanine, phenylglycine, canavanine, canaline, 4-hydroxyarginine,4-hydroxyornithine, homoarginine, 4-hydroxyhomoarginine, β-lysine,2,4-diaminobutanoic acid, 2,3-diaminopropanoic acid, 2,6-diaminopimelicacid, 2-amino-3-phenylbutanoic acid 2-methylserine, 3-phenylserine,betaine, taurine, cysteinesulfinic acid, methionine sulfoxide,methionine sulfone, 3,5-diiodotyrosine, thyroxine, monoiodotyrosine,pipecolic acid, 4-aminopipecolic acid, 4-methylproline, glycylglycine,carnosine, anserine, ophidine, homocarnosine, β-alanyllysine,β-alanylarginine, glutathione, opththalmic acid, norophthalmic acid,bradykinin, glucagon, protamines, histones, cocoamphoglycine,cocoamphopropionate, cocoamphopropylsulfonate, phosphatidylethanolamine, phosphatidyl serine, sphingomyelin, stearamidoethyldiethylamine, stearamidoethyl diethanolamine, stearamidopropyldimethylamine, quaternary ammonium hyroxide, quaternium hydroxide,aluminum oxide or zinc oxide.
 17. The composition of claim 12 whereinsaid alpha hydroxyacid is an alkyl alpha hydroxyacid, aralkyl and arylalpha hydroxyacid, polyhydroxy alpha hydroxyacid or polycarboxylic alphahydroxyacid having the following chemical formula: (Ra) (Rb) C (OH) COOHwherein Ra and Rb are H, F. Cl, Br, alkyl, aralkyl or aryl group ofsaturated or unsaturated, isomeric or non-isomeric, straight or branchedchain or cyclic form, having 1 to 25 carbon atoms, and in addition Raand Rb may carry OH, CHO, COOH and alkoxy group having 1 to 9 carbonatoms. The alpha hydroxyacid may exist as a free acid or lactone form,or in salt form with an organic base or an inorganic alkali, and asstereoisomers as D, L, and DL forms when Ra and Rb are not identical.18. The composition of claim 17 wherien said alkyl alpha hydroxyacid isselected from the group consisting of 2-Hydroxyethanoic acid (Glycolicacid), 2-Hydroxypropanoic acid (Lactic acid), 2-Methyl2-hydroxypropanoic acid (Methyllactic acid), 2-Hydroxybutanoic acid,2-Hydroxypentanoic acid, 2-Hydroxyhexanoic acid, 2-Hydroxyheptanoicacid, 2-Hydroxyoctanoic acid, 2-Hydroxynonanoic acid, 2-Hydroxydecanoicacid, 2-Hydroxyundecanoic acid, 2-Hydroxydodecanoic acid (Alphahydroxylauric acid), 2-Hydroxytetradecanoic acid (Alpha hydroxymyristicacid), 2-Hydroxyhexadecanoic acid (Alpha hydroxypalmitic acid),2-Hydroxyoctadecanoic acid (Alpha hydroxystearic acid),2-Hydroxyeicosanoic acid (Alpha hydroxyarachidonic acid).
 19. Thecomposition of claim 17 wherein said aralkyl and aryl alpha hydroxyacidis selected from the group consisting of 2-Phenyl 2-hydroxyethanoic acid(Mandelic acid), 2,2-Diphenyl 2-hydroxyethanoic acid (Benzilic acid),3-Phenyl 2-hydroxypropanoic aicid (Phenyllactic acid), 2-Phenyl 2-methyl2-hydroxyethanoic acid (Atrolactic acid), 2-(4′-Hydroxyphenyl)2-hydroxyehtanoic acid, 2-(4′-Chlorophenyl) 2-hydroxyethanoic acid,2-(3′-Hydroxy-4′-methoxyphenyl) 2-hydroxyethanonic acid,2-(4′-Hydroxy-3′-methoxyphenyl) 2-hydroxyethanoic acid,3-(2′-Hydroxyphenyl) 2-hydroxypropanoic acid, 3-(4′-Hydroxyphenyl)2-hydroxypropanoic acid, or 2-(3′,4′-Dihydroxyphenyl) 2-hydroxyethanoicacid.
 20. The composition of claim 17 wherein said polyhydroxy alphahydroxyacid or polycarboxylic alpha hydroxyacid is selected from thegroup consisting of 2,3-Dihydroxypropanoic acid (Glyceric acid),2,3,4-Trihydroxybutanoic acid (Isomers; erythronic acid, threonic acid),2,3,4,5-Tetrahydroxypentanoic acid (Isomers; ribonic acid, arabinoicacid, xylonic acid, lyxonic acid) 2,3,4,5,6-Pentahydroxyhexanoic acid(Isomers; allonic acid, altronic acid, gluconic acid, mannoic acid,gulonic acid, idonic acid, galactonic acid, talonic acid),2,3,4,5,6,7-Hexahydroxyheptanoic acid (Isomers; glucoheptonic acid,galactoheptonic acid, etc.), 2-Hydroxypropane-1,3-dioic acid (tartronicacid), 2-Hydroxybutane-1,4-dioic acid (Malic acid),2,3-Dihydroxybutane-1,4-dioic acid (Tartaric acid),2-Hydroxy-2-carboxypentane-1,5-dioic acid (Citric acid),2,3,4,5-Tetrahydroxyhexane-1,6-dioic acid (Isomers; saccharic acid,mucic acid, etc.), or lactone forms (gluconolactone, galactonolactone,glucuronolactone, galacturonolactone, gulonolactone, ribonolactone,saccharic acid lactone, pantoyllactone, glucoheptonolactone,mannonolactone, galactoheptonolactone, etc.)
 21. The composition ofclaim 12 wherein said alpha ketoacid is selected from a group ofcompounds having chemical formula: (Ra) CO COO(Rb) wherein Ra and Rb areH, alkyl, aralkyl or aryl group of saturated or unsaturated, isomeric ornon-isomeric, straight or branched chain or cyclic form, having 1 to 25carbon atoms, and in addition Ra may carry F, Cl, Br, I, OH, CHO, COOHand alkoxy group having 1 to 9 carbon atoms, said alpha ketoacidexisting as a free acid or an ester form, or in a salt form with anorganic base or an inorganic alkali.
 22. The composition of claim 21wherein said alpha ketoacid and its ester is a member selected from thegroup consisting of 2-Ketoethanoic acid (Glyoxylic acid), Methyl2-ketoethanoate, 2-Ketopropanoic acid (Pyruvic acid), Methyl2-ketopropanoate (Methyl pyruvate), Ethyl 2-ketopropanoate (Ethylpyruvate), Propyl 2-ketopropanoate (Propyl pyruvate),2-Phenyl-2-ketoethanoic acid (Benzoylformic acide), Methyl2-phenyl-2-ketoethanoate (Methyl benzoylformate), Ethyl2-phenyl-2-ketoethanoate (Ethyl benzoylformate),3-Phenyl-2-ketopropanoic acid (Phenylpyruvic acid), Methyl3-phenyl-2-ketopropanoate (methylphenylpyruvate), Ethyl3-phenyl-2-ketopropanoate (Ethyl phenylpyruvate), 2-Ketobutanoic acid,2-Ketopentanoic acid, 2-Ketohexanoic acid, 2-Ketoheptanoic acid,2-Ketooctanoic acid, 2-Ketododecanoic acid, or Methyl 2-Ketooctanoate.23. The composition of claim 12 wherein said the related compound isselected from the group consisting of ascorbic acid, quinic acid,isocitric acid, tropic acid, trethocanic acid, 3-chlorolactic acid,cerebronic acid, citramalic acid, agaricic acid, 2-hydroxynervonic acid,aleuritic acid and pantoic acid.
 24. The composition of claim 12 whereinsaiod cosmetic conditions and medical disorders include dry skin,zerosis, ichthyosis, dandruff, brownish spots, keratoses, melasma,lentigines, age spots, liver spots, pigmented spots, wrinkles,blemishes, skin lines, oily skin, acne, warts, exzema, purutic skin,psoriasis, inflammatory dermatoses, distubted keratinization, skinchanges associated with aging, nail or skin requiring cleansers,conditioning or treatment, and hair requiring conditioning orshampooing.
 25. A therapeutic composition for topical treatment ofwarts, nail infections, age spots, wrinkles and aging related skinchanges comprising at least one member selected from the groupconsisting of alpha hydroxyacids, alpha ketoacids or related compounds.26. The composition of claim 25 wherein said alpha hydroxyacids, alphaketoacids and the related compounds may be present as a free acid,lactone, ester or in salt form with an organic base or an inorganicalkali.
 27. The composition of claim 25 wherein said alpha hydroxyacids,alpha ketoacids or related compounds are selected from the groupconsisting of 2-hydroxyethanoic acid, 2-hydroxypropanoic acid, 2-methyl2-hydroxypropanoic acid, 2-phenyl 2-hydroxyethanoic acid, 2,2-diphenyl2-hydroxyethanoic acid, 2-phenyl 2-methyl 2-hyroxyethanoic acid,2-phenyl 3-hydroxypropanoic acid, 2-ketopropanoic acid, methyl2-ketopropanoate and ethyl 2-ketopropanoate.
 28. Method of topicaltreatment for warts, nail infections, age spots, wrinkles and agingrelated skin changes comprising topically supplying a therapeuticallyeffective amount of at least one member selected from the groupconsisting of alpha hydroxyacids, alpha ketoacids and the relatedcompounds in a pharmaceutically acceptable vehicle.
 29. The method ofclaim 28 wherein said alpha hydroxyacids, alpha ketoacids and therelated compounds may be present as a free acid, lactone, ester or insalt form with an organic base or inorganic alkali.
 30. The method ofclaim 27 wherien said alpha hyroxyacids, alpha ketoacids or relatedcompound is selected from the group consisting of 2-hydroxyethanoicacid, 2-hydroxypropanoic acid, 2-methyl 2-hydroxypropanoic acid,2-phenyl 2-hydroxyethanoic acid, 2,2-diphenyl 2-hydroxyethanoic acid,2-phenyl 2-methyl 2-hydroxyethanoic acid, 2-phenyl 3-hydroxypropanoicacid, 2-ketopropanoic acid, methyl 2-ketopropanoate or ethyl2-ketopropanoate.
 31. A therapeutic composition for topical treatment ofcosmetic conditions or dermatologic disorders comprising dimeric orpolymeric forms of hydroxyacids, having the following chemical formula:H [C—O—C(Ra) (Rb)—CO—]n OH wherein Ra,Rb=H, alkyl, aralkyl or aryl groupof saturated or unsaturated, isomeric or non-isomeric, straight orbranched hain or cyclic form, having 1 to 25 carbon atoms, and n=1 orany numerical number up to 200, Ra and Rb in monomer unit 2, 3, 4 may bethe same or the different groups from that in monomer unit 1; thehydrogen atom in Ra and Rb may be substituted by a halogen atom or aradical of lower alkyl, aralkyl, aryl or alkoxy of saturated orunsaturated, isomeric or non-isomeric, straight or branched chain orcyclic form, having 1 to 9 carbon atoms, and the dimeric and polymericforms of hydroxyacids may be present as a free acid, ester or in a saltform with an organioc base or inorganic alkali.
 32. The composition ofclaim 31 wherein said dimeric or polymeric forms of hydroxyacids areselected from the group consistinf of glycolyl glycollate, lactyllactate, mandelyl mandellate, atrolactyl atrolactate, phenyllactylphenyllactate, benzilyl benzillate, glycolyl lactate, lactyl glycollate,triglycolic acid, trilactic acid, polyglycolic acid or polylactic acid.33. The composition of claim 31 further comprising a cosmetic orpharmaceutic agent incorporated as a combination ingredient in saidcomposition.
 34. A therapeutic composition for topical treatment ofcosmetic conditions or dermatologic disorders comprising dimeric orpolymeric forms of hydroxyacids, having the following chemical formula:[—O—C(Ra) (Rb)—CO—]n wherein Ra,Rb=H, alkyl, aralky or aryl group ofsaturated or unsaturated, isomeric or non-isomeric, straight or branchecchain or cyclic form, having 1 to 25 carbon atoms, and n=1 or anynumerical number, and Ra or Rb may be identical or not identical in themonomer units.
 35. The composition of claim 34 wherein said dimeric orpolymeric forms of hydroxcyacids are selected from the group consistinfgof glycolide, lactide, mandelide, atrolactide, phenyllactide, benzilide,methyllactide, lactoglycolide or glycolactide.
 36. The composition ofclaim 34 further comprising a cosmetic or pharmaceutic agentincorporated as a combination ingredients in said composition.
 37. Amethod of treatment to alleviate cosmetic conditions and/or dermatologicdisorders comprising in combination an amphoteric or pseudoamphotericagent and an alpha hydroxyacid, an alpha ketoacid or the relatedcompound in a cosmetically or pharmaceutically acceptable vehicle. 38.The method of claim 37 further comprising a cosmetic or pharmaceuticagent incorporated as a combination ingredient in said composition. 39.A method of treatment to alleviate cosmetic conditions and/ordermatologic disorders comprising dimeric or polymeric forms ofhydroxyacids with or without in combination with an amphoteric orpseudoamphoteric agent in a cosmetically or pharmaceutically acceptablevehicle.
 40. The method of claim 39 further comprising a cosmetic orpharmaceutic agent incorporated as a combination ingredient in saidcomposition.